Palbociclib and Binimetinib in RAS-Mutant Cancers, A ComboMATCH Treatment Trial

Phase 2

Recruiting

• Conditions: Ovarian Low Grade Serous Adenocarcinoma; Exocrine Pancreas Carcinoma; Stage IV Ovarian Cancer AJCC v8; Malignant Solid Neoplasm; Stage IV Pancreatic Cancer AJCC v8
• Interventions: Drug: Binimetinib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Palbociclib

• Registration Number: NCT05554367
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase II ComboMATCH treatment trial evaluates the effectiveness of palbociclib and binimetinib in treating patients with RAS-mutated cancers. Palbociclib and binimetinib are both in a class of medications called kinase inhibitors. They work by blocking the action of abnormal proteins that signals cancer cells to multiply. This trial may help researchers understand if giving the combination of palbociclib and binimetinib can help improve the amount of time before the cancer grows in patients with patients with low grade serous ovarian cancer who have certain changes in the tumor DNA. This trial may also help researchers understand if giving the combination of palbociclib and binimetinib can help improve outcomes among patients with low grade serous ovarian cancer who have previously received a MEK inhibitor. For patients with other tumors, with the exception of lung cancer, colon cancer, melanoma and low grade serous ovarian cancers, this trial may help researchers understand if giving the combination of palbociclib and binimetinib can improve the clinical outcome of survival without progression in patients who have certain changes in their tumor's DNA.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether palbociclib and binimetinib combination therapy improves progression free survival (PFS) compared to binimetinib alone in patients with MEK-inhibitor naive low-grade serous ovarian cancer (LGSOC) harboring MAP kinase activation (KRAS/NRAS/non BRAF V600E mutation). (Cohort 1) II. To determine whether palbociclib and binimetinib improves clinical activity in comparison to historical control, as measured by objective response rate (ORR), in women with LGSOC whose disease has previously progressed on a MEK inhibitor. (Cohort 2) III. To determine whether palbociclib and binimetinib combination therapy improves the objective response rate compared to historical control in patients with pancreatic cancer harboring any KRAS/NRAS/HRAS mutation or non-BRAF V600E aMOIs or rare RAF fusion. (Cohort 3) IV. To determine whether palbociclib and binimetinib combination therapy improves objective response rate compared to historical control in patients with tumors harboring any KRAS/NRAS/HRAS mutations or non-BRAF V600E aMOIs or rare RAF fusions (excluding LGSOC, non-small cell lung cancer \[NSCLC\], colorectal cancer, pancreatic cancer and melanoma). (Cohort 4)

SECONDARY OBJECTIVES:

I. To determine whether palbociclib and binimetinib combination therapy improves objective response rate (ORR), overall survival (OS), duration of response (DOR), and disease control rate (DCR) compared to binimetinib alone in patients with MEK inhibitor-naïve LGSOC. (Cohort 1) II. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 1) III. To assess the clinical activity of palbociclib and binimetinib as measured by PFS, OS, DOR, and DCR in women with LGSOC whose disease has previously progressed on a MEK inhibitor. (Cohort 2) IV. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 2) V. To assess the clinical activity of palbociclib and binimetinib as measured by PFS, OS, DOR, and DCR in patients with RAS mutated pancreatic cancer. (Cohort 3) VI. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 3) VII. To assess the clinical activity of palbociclib and binimetinib as measured by PFS, OS, DOR, and DCR in patients with RAS mutated cancers, excluding LGSOC, NSCLC, colorectal cancer (CRC), pancreatic cancer and melanoma. (Cohort 4) VIII. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 4)

EXPLORATORY OBJECTIVES:

I. Explore thymidine kinase 1 (TK1) activity in response to palbociclib. (Cohort 1) II. Assess the correlation between presence of KRAS mutation and activity of both monotherapy and the combination. (Cohort 1) III. Conduct ribonucleic acid (RNA)-sequencing (seq) to assess determinants of response and resistance. (Cohort 1) IV. Explore changes in plasma RAS allelic burden in KRAS-mutated tumors using circulating tumor deoxyribonucleic acid (ctDNA) and correlate changes with clinical activity. (Cohort 1) V. Explore TK1 activity in response to palbociclib.(Cohort 2) VI. Assess the correlation between presence of KRAS mutation and activity of the combination. (Cohort 2) VII. Conduct RNA-seq to assess determinants of response and resistance. (Cohort 2) VIII. Explore changes in plasma RAS allelic burden in KRAS-mutated tumors using ctDNA and correlate changes with clinical activity. (Cohort 2) IX. Explore TK1 activity in response to palbociclib. (Cohort 3) X. Evaluate changes in deoxyribonucleic acid (DNA), RNA and ctDNA to evaluate concordance with the designated laboratory result and to assess determinants of response, signatures of intrinsic resistance or response and the plasma RAS allelic burden in relation to treatment response, respectively. (Cohort 3) XI. Explore TK1 activity in response to palbociclib. (Cohort 4) XII. Evaluate changes in DNA, RNA and ctDNA to evaluate concordance with the designated laboratory result and to assess determinants of response, signatures of intrinsic resistance or response and the plasma RAS allelic burden in relation to treatment response, respectively. (Cohort 4)

OUTLINE: Patients with KRAS, NRAS, non-BRAF V600E aMOIs or rare RAF fusions LGSOC, naïve to MEK or CDK4/6 inhibitor therapy are randomized to either combination cohort 1 or monotherapy cohort 1. Patients with LGSOC who have received prior MEK inhibitor therapy are assigned to combination cohort 2. Patients with KRAS/NRAS/HRAS/non-V600E a MOIs or rare RAF fusion pancreatic cancer are assigned to combination cohort 3. Patients with all other KRAS/NRAS/HRAS, non -BRAF V600E a MOIs or rare FAR fusion tumor types (excluding LGSOC, NSCLC, CRC, pancreatic, and melanoma) are assigned to combination cohort 4.

COMBINATION COHORTS 1, 2, 3, 4: Patients receive palbociclib orally (PO), once per day (QD) on days 1-21 and binimetinib PO twice per day (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo magnetic resonance imaging (MRI), computed tomography (CT), bone scan, and collection of blood samples during screening, on study, and/or during follow up.

MONOTHERAPY COHORT 1: Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

After completion of study treatment, patients are followed up every 3 months for up to 3 years following registration.

Study Timeline

• Study First Submitted: 2022-09-22
• Study First Submitted QC: 2022-09-22
• Study First Posted: 2022-09-26
• Study Start: 2023-12-13
• Status Verified: 2024-12
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-15
• Primary Completion: 2026-08-26
• Study Completion: 2026-08-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 199

Inclusion Criteria

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-A3 based on the presence of an actionable mutation as defined in EAY191.

• GENERAL ComboMATCH EAY191 REGISTRATION INCLUSION CRITERIA:

• Patients must be enrolled on the EAY191 registration study and be assigned to this protocol by EAY191

• Patients must have KRAS/NRAS/HRAS or RAF mutations or rare RAF fusions as determined by the ComboMATCH screening assessment

• Patients with low grade serous ovarian cancer who have progressed on a prior MEK inhibitor are not required to have a KRAS/NRAS/HRAS or BRAF alteration

• Patients must not have a BRAF V600E alteration as determined by the ComboMATCH screening assessment

• Patients with a tumor harboring KRAS G12C mutation will be eligible either after they have received a G12C inhibitor or can be enrolled if they do not meet eligibility for a G12C inhibitor. However, patients with tumors harboring KRAS G12C mutation will be prioritized for a G12C inhibitor-based substudy if eligible

• Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to registration

• Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website

• EAY191-A3 IELIGIBILITY CRITERIA:

• Histologically confirmed cancer for each cohort for which curable treatment modalities are not an option. Rare BRAF fusions and non-BRAF V600E aMOIs are acceptable. RB1 mutations or two copy RB1 deletions are excluded

• Tumor tissue must be available:

  • Adequate archival tumor specimen (obtained within 12 months of EAY191 registration which has not had a Response Evaluation Criteria in Solid Tumors (RECIST) response, complete response (CR) or partial response (PR), to any intervening therapy after collection of the tissue) must be available with formalin-fixed paraffin-embedded tumor tissue (blocks or slides) OR
  • Consent to a new tumor tissue biopsy which is not a representative target lesion. This lesion must be amenable to a minimal risk image-guided or direct vision biopsy A new biopsy is preferred but is not required for enrollment in EAY191-A3 if sufficient archival tissue is available as described above

• Measurable disease per RECIST 1.1. Of note, in the case when a baseline biopsy is done after scans are obtained, a lesion separate from one that is biopsied needs to be measurable per RECIST 1.1. All radiologic studies must be performed within 28 days prior to registration

• COHORT 1: Low grade serous ovarian cancer with KRAS, NRAS non-BRAF V600E aMOIs or rare RAF fusions are acceptable

• COHORT 1: No prior MEK inhibitor or CDK4/6 inhibitor therapy

• COHORT 1: Any number of prior therapies permitted

• COHORT 1: No major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 2 weeks prior to registration

• COHORT 1: No prior cancer-directed therapy within 28 days prior to registration. Patients may have received cancer-directed hormonal therapy up to 14 days prior to registration

• COHORT 2: Low grade serous ovarian cancer

• COHORT 2: Prior progression of disease on a MEK inhibitor (prior binimetinib permitted)

• COHORT 2: If patient has previously received binimetinib, they cannot have required dose reduction or discontinuation of binimetinib due to adverse events

• COHORT 2: No prior receipt of a CDK4/6 inhibitor

• COHORT 2: No major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 2 weeks prior to registration

• COHORT 2: No prior cancer-directed therapy within 28 days prior to registration. Patients may have received cancer-directed hormonal therapy up to 14 days prior to registration

• COHORT 3: Pancreatic cancer with KRAS/NRAS/HRAS, non-BRAF V600E aMOIs or rare RAF fusions are acceptable

• COHORT 3: No prior MEK inhibitor (MEKi) and CDK4/6i therapy

• COHORT 3: Progression after at least one line of prior therapy as long as there is no standard therapy available or acceptable to patients that is thought to be of benefit

• COHORT 3: Any number of prior therapies are permitted

• COHORT 3: No major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 2 weeks prior to registration

• COHORT 3: No prior cancer-directed therapy within 28 days prior to registration. Patients may have received cancer-directed hormonal therapy up to 14 days prior to registration

• COHORT 4: KRAS/NRAS/HRAS non-BRAF V600E aMOIs or rare RAF fusions are acceptable

• COHORT 4: No prior MEKi and CDK4/6i therapy and progression after at least one line of prior therapy, as long as there is no standard therapy available or acceptable to patients that is thought to be of benefit

• COHORT 4: Any number of prior therapies are permitted

• COHORT 4: No more than 6 patients with a given tumor type allowed in this cohort

• COHORT 4: Any tumor type, except: LGSOC/NSCLC/CRC/pancreatic/melanoma

• COHORT 4: No major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 2 weeks prior to registration

• COHORT 4: No prior cancer-directed therapy within 28 days prior to registration. Patients may have received cancer-directed hormonal therapy up to 14 days prior to registration

• Not pregnant and not nursing, because this study involves investigational agents whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status < 2

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin > 9 g/dL

• Creatinine =< 1.5 x upper limit of normal (ULN) or calculated (calc.) creatinine clearance >= 30 mL/min as calculated by the Cockcroft-Gault formula

• Total bilirubin =< 1.5 x upper limit of normal (ULN). Patients with Gilbert syndrome may enroll if total bilirubin (bili) < 3 mg/dL (51 micromole/L)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

• Creatine phosphokinase (CPK) =< 2.5 x ULN

• Patients must be able to swallow oral formulations of the agents

• No history of interstitial lung disease. No history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

• Patients should not have history of bowel perforation or intestinal fistulas in the last 6 months

• No patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease

• No active skin disorder that has required systemic therapy within the past 1 year

• No history of rhabdomyolysis

• No concurrent ocular disorders including:

  • Subjects with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes
  • Subject with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO
  • Subjects with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions

• No patients with a history of hypersensitivity to any of the study drug(s)

• No prior allogeneic stem cell or solid organ transplantation

• Central nervous system (CNS) metastases must have been treated with local therapy (surgery, radiation, ablation) and patient off of systemic steroids, and brain metastases stable for at least 1 month

• No residual Common Terminology Criteria for Adverse Events (CTCAE) >= grade 2 toxicity from any prior anticancer therapy, with the exception of grade 2 alopecia

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients whose left ventricular ejection fraction (LVEF) has been evaluated by echocardiography (ECHO)/multigated acquisition scan (MUGA) are excluded if the most recent exam shows an LVEF < 50%

• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study

• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment

• No exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and during the course of therapy

• Patients treated with Cohort 1 control treatment binimetinib who experience disease progression may elect to migrate to cohort 2 and receive combination treatment with palbociclib and binimetinib. Patients who choose to do so must meet laboratory values and performance status requirements as above and must be begin treatment within 21 days. For patients who migrate from cohort 1 to cohort 2, the 28-day window restricting prior anti-cancer directed therapies does not apply to prior binimetinib. A new biopsy will not be required for migration, but the optional biopsy at disease progression should be encouraged

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)	Binimetinib	Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)	Biospecimen Collection	Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)	Bone Scan	Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)	Biopsy Procedure	Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)	Computed Tomography	Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)	Magnetic Resonance Imaging	Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)	Palbociclib	Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Monotherapy Cohort 1 (binimetinib)	Binimetinib	Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Monotherapy Cohort 1 (binimetinib)	Biopsy Procedure	Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Monotherapy Cohort 1 (binimetinib)	Biospecimen Collection	Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Monotherapy Cohort 1 (binimetinib)	Bone Scan	Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Monotherapy Cohort 1 (binimetinib)	Computed Tomography	Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Monotherapy Cohort 1 (binimetinib)	Magnetic Resonance Imaging	Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

Primary Outcome Measures

Name	Time	Method
ORR (Cohort 3)	Up to 3 years	The Simon minimax design used to evaluate efficacy in terms of the objective response rate after treatment in this population will use a two-stage design.
Progression free survival (PFS) (Cohort 1)	Time from randomization date until the time of disease progression or death due to any cause, assessed at 6, 12, 18, 24, and 30 months	Will compare the PFS distributions between those treated with palbociclib and binimetinib vs. binimetinib alone. PFS will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median PFS, and estimated PFS rates at 6, 12, 18, 24, and 30 months will be estimated along with corresponding 95% confidence intervals. A log-rank test will be used to compare the PFS distributions between the two treatment arms in this cohort. In an ancillary manner, Cox proportional hazards models will also be used to assess the impact of treatment arm on PFS when stratifying on the stratification factors.
Objective response rate (ORR) (Cohort 2)	Up to 3 years	The Simon optimal design used to evaluate efficacy in terms of the objective response rate after treatment in this population will use a two-stage design.
ORR (Cohort 4)	Up to 3 years	The Simon minimax design used to evaluate efficacy in terms of the objective response rate after treatment in this histology/tumor agnostic population will use a two-stage design.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS) (All Cohorts)	From registration until death due to any cause, assessed up to 3 years	Patients who are alive at last follow-up will be censored at that time point. The distribution of OS will be estimated using method of Kaplan-Meier. The median OS and 95% confidence interval will be reported.
Disease control (All Cohorts)	Up to 3 years	Disease control will be estimated using disease control rate (DCR), which is defined as the patients who experience CR or PR per RECIST 1.1 or maintain stable disease for at least 6 months after randomization divided by the total number of evaluable patients. DCR will be evaluated within cohorts, and for cohort 1 this will also be compared between treatment arms using a chi square test. Point estimates will be generated for disease control rates within each arm along with 95% confidence intervals using the Clopper-Pearson method.
Objective response (Cohort 1)	Up to 3 years	Objective response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria will be estimated using ORR where ORR is defined as the number of evaluable patients achieving a response (partial response \[PR\] or complete response \[CR\] per RECIST v1.1) during treatment with study therapy divided by the total number of evaluable patients. Rates of response will be compared between treatment arms using a chi-square test (or Fisher's exact test as needed). Point estimates will be generated for objective response rates within each arm along with 95% confidence intervals using the Clopper-Pearson method.
PFS (Cohorts 2, 3, 4)	From study entry to the first of either disease progression or death from any cause, assessed up to 3 years	Disease progression will be determined based on RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and corresponding 95% confidence interval will be reported. Patients will be censored at the last disease assessment date if they were alive and progression-free at the time of their last assessment.
Duration of response (DoR) (All Cohorts)	From patient's earliest best objective status to earliest date of progression, assessed up to 3 years	DoR is defined for all evaluable patients who have achieved an objective response as time from the patient's earliest best objective status is first noted as either a CR or PR to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier.
Incidence of adverse events (AE) (All Cohorts)	Up to 3 years	All eligible patients that have initiated treatment will be considered evaluable for assessing AE rate(s). Patients will be evaluated for adverse events using the National Cancer Institute's Common Toxicity Criteria for Adverse Events version 5.0. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the AE(s) to the study treatment will be taken into consideration.

Trial Locations

Locations (263)

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Carle Physician Group-Mattoon/Charleston; 🇺🇸 Mattoon, Illinois, United States

Illinois CancerCare - Washington; 🇺🇸 Washington, Illinois, United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic; 🇺🇸 Ankeny, Iowa, United States

University of South Alabama Mitchell Cancer Institute; 🇺🇸 Mobile, Alabama, United States

UC San Diego Health System - Encinitas; 🇺🇸 Encinitas, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Cancer Care Center of O'Fallon; 🇺🇸 O'Fallon, Illinois, United States

Advocate Christ Medical Center; 🇺🇸 Oak Lawn, Illinois, United States

Advocate Outpatient Center - Oak Lawn; 🇺🇸 Oak Lawn, Illinois, United States

Mercy Hospital; 🇺🇸 Cedar Rapids, Iowa, United States

VA Palo Alto Health Care System; 🇺🇸 Palo Alto, California, United States

UC San Diego Medical Center - Hillcrest; 🇺🇸 San Diego, California, United States

Northwestern Medicine Orland Park; 🇺🇸 Orland Park, Illinois, United States

University of Chicago Medicine-Orland Park; 🇺🇸 Orland Park, Illinois, United States

Oncology Associates at Mercy Medical Center; 🇺🇸 Cedar Rapids, Iowa, United States

UCHealth University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Poudre Valley Hospital; 🇺🇸 Fort Collins, Colorado, United States

Illinois CancerCare-Ottawa Clinic; 🇺🇸 Ottawa, Illinois, United States

Advocate High Tech Medical Park; 🇺🇸 Palos Heights, Illinois, United States

Advocate Lutheran General Hospital; 🇺🇸 Park Ridge, Illinois, United States

Illinois CancerCare-Pekin; 🇺🇸 Pekin, Illinois, United States

Illinois CancerCare-Peoria; 🇺🇸 Peoria, Illinois, United States

Illinois CancerCare-Peru; 🇺🇸 Peru, Illinois, United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic; 🇺🇸 Des Moines, Iowa, United States

UI Health Care Mission Cancer and Blood - Waukee Clinic; 🇺🇸 Waukee, Iowa, United States

Cancer Care and Hematology-Fort Collins; 🇺🇸 Fort Collins, Colorado, United States

UCHealth Greeley Hospital; 🇺🇸 Greeley, Colorado, United States

Medical Center of the Rockies; 🇺🇸 Loveland, Colorado, United States

UM Sylvester Comprehensive Cancer Center at Aventura; 🇺🇸 Aventura, Florida, United States

Illinois CancerCare-Princeton; 🇺🇸 Princeton, Illinois, United States

Mercyhealth Cancer Institute - Rockford; 🇺🇸 Rockford, Illinois, United States

University of Kentucky/Markey Cancer Center; 🇺🇸 Lexington, Kentucky, United States

Harold Alfond Center for Cancer Care; 🇺🇸 Augusta, Maine, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables; 🇺🇸 Coral Gables, Florida, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach; 🇺🇸 Deerfield Beach, Florida, United States

University of Florida Health Science Center - Gainesville; 🇺🇸 Gainesville, Florida, United States

Southern Illinois University School of Medicine; 🇺🇸 Springfield, Illinois, United States

Springfield Clinic; 🇺🇸 Springfield, Illinois, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Kendall; 🇺🇸 Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Plantation; 🇺🇸 Plantation, Florida, United States

Saint Alphonsus Cancer Care Center-Boise; 🇺🇸 Boise, Idaho, United States

Saint Luke's Cancer Institute - Boise; 🇺🇸 Boise, Idaho, United States

Saint Alphonsus Cancer Care Center-Caldwell; 🇺🇸 Caldwell, Idaho, United States

Kootenai Health - Coeur d'Alene; 🇺🇸 Coeur d'Alene, Idaho, United States

Saint Luke's Cancer Institute - Fruitland; 🇺🇸 Fruitland, Idaho, United States

Saint Luke's Cancer Institute - Meridian; 🇺🇸 Meridian, Idaho, United States

Saint Alphonsus Cancer Care Center-Nampa; 🇺🇸 Nampa, Idaho, United States

Saint Luke's Cancer Institute - Nampa; 🇺🇸 Nampa, Idaho, United States

Kootenai Clinic Cancer Services - Post Falls; 🇺🇸 Post Falls, Idaho, United States

Kootenai Clinic Cancer Services - Sandpoint; 🇺🇸 Sandpoint, Idaho, United States

Advocate Good Shepherd Hospital; 🇺🇸 Barrington, Illinois, United States

Illinois CancerCare-Bloomington; 🇺🇸 Bloomington, Illinois, United States

Illinois CancerCare-Canton; 🇺🇸 Canton, Illinois, United States

Illinois CancerCare-Carthage; 🇺🇸 Carthage, Illinois, United States

Springfield Memorial Hospital; 🇺🇸 Springfield, Illinois, United States

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

John H Stroger Jr Hospital of Cook County; 🇺🇸 Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

Advocate Illinois Masonic Medical Center; 🇺🇸 Chicago, Illinois, United States

AMG Crystal Lake - Oncology; 🇺🇸 Crystal Lake, Illinois, United States

Carle at The Riverfront; 🇺🇸 Danville, Illinois, United States

Cancer Care Specialists of Illinois - Decatur; 🇺🇸 Decatur, Illinois, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Northwestern Medicine Cancer Center Kishwaukee; 🇺🇸 DeKalb, Illinois, United States

Illinois CancerCare-Dixon; 🇺🇸 Dixon, Illinois, United States

Advocate Good Samaritan Hospital; 🇺🇸 Downers Grove, Illinois, United States

Carle Physician Group-Effingham; 🇺🇸 Effingham, Illinois, United States

Crossroads Cancer Center; 🇺🇸 Effingham, Illinois, United States

Advocate Sherman Hospital; 🇺🇸 Elgin, Illinois, United States

Illinois CancerCare-Eureka; 🇺🇸 Eureka, Illinois, United States

Illinois CancerCare-Galesburg; 🇺🇸 Galesburg, Illinois, United States

Northwestern Medicine Cancer Center Delnor; 🇺🇸 Geneva, Illinois, United States

Advocate South Suburban Hospital; 🇺🇸 Hazel Crest, Illinois, United States

Northwestern Medicine Glenview Outpatient Center; 🇺🇸 Glenview, Illinois, United States

Northwestern Medicine Grayslake Outpatient Center; 🇺🇸 Grayslake, Illinois, United States

Northwestern Medicine Cancer Center Warrenville; 🇺🇸 Warrenville, Illinois, United States

Illinois CancerCare-Kewanee Clinic; 🇺🇸 Kewanee, Illinois, United States

Northwestern Medicine Lake Forest Hospital; 🇺🇸 Lake Forest, Illinois, United States

UC Comprehensive Cancer Center at Silver Cross; 🇺🇸 New Lenox, Illinois, United States

AMG Libertyville - Oncology; 🇺🇸 Libertyville, Illinois, United States

Condell Memorial Hospital; 🇺🇸 Libertyville, Illinois, United States

Illinois CancerCare-Macomb; 🇺🇸 Macomb, Illinois, United States

Lafayette Family Cancer Center-EMMC; 🇺🇸 Brewer, Maine, United States

MaineHealth Maine Medical Center- Scarborough; 🇺🇸 Scarborough, Maine, United States

MaineHealth Cancer Care and IV Therapy - South Portland; 🇺🇸 South Portland, Maine, United States

University of Maryland/Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States

UPMC Western Maryland; 🇺🇸 Cumberland, Maryland, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor; 🇺🇸 Ann Arbor, Michigan, United States

Bronson Battle Creek; 🇺🇸 Battle Creek, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health Medical Center - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton; 🇺🇸 Canton, Michigan, United States

Trinity Health Medical Center - Canton; 🇺🇸 Canton, Michigan, United States

Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Corewell Health Dearborn Hospital; 🇺🇸 Dearborn, Michigan, United States

OSF Saint Francis Hospital and Medical Group; 🇺🇸 Escanaba, Michigan, United States

Corewell Health Farmington Hills Hospital; 🇺🇸 Farmington Hills, Michigan, United States

Cancer Hematology Centers - Flint; 🇺🇸 Flint, Michigan, United States

Genesee Hematology Oncology PC; 🇺🇸 Flint, Michigan, United States

Genesys Hurley Cancer Institute; 🇺🇸 Flint, Michigan, United States

Hurley Medical Center; 🇺🇸 Flint, Michigan, United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital; 🇺🇸 Grand Rapids, Michigan, United States

Trinity Health Grand Rapids Hospital; 🇺🇸 Grand Rapids, Michigan, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

Ascension Borgess Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

University of Michigan Health - Sparrow Lansing; 🇺🇸 Lansing, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital; 🇺🇸 Livonia, Michigan, United States

Trinity Health Muskegon Hospital; 🇺🇸 Muskegon, Michigan, United States

Corewell Health Lakeland Hospitals - Niles Hospital; 🇺🇸 Niles, Michigan, United States

Cancer and Hematology Centers of Western Michigan - Norton Shores; 🇺🇸 Norton Shores, Michigan, United States

Michigan Healthcare Professionals Pontiac; 🇺🇸 Pontiac, Michigan, United States

Trinity Health Saint Joseph Mercy Oakland Hospital; 🇺🇸 Pontiac, Michigan, United States

Corewell Health Reed City Hospital; 🇺🇸 Reed City, Michigan, United States

Corewell Health William Beaumont University Hospital; 🇺🇸 Royal Oak, Michigan, United States

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center; 🇺🇸 Saint Joseph, Michigan, United States

Corewell Health Lakeland Hospitals - Saint Joseph Hospital; 🇺🇸 Saint Joseph, Michigan, United States

Munson Medical Center; 🇺🇸 Traverse City, Michigan, United States

Corewell Health Beaumont Troy Hospital; 🇺🇸 Troy, Michigan, United States

University of Michigan Health - West; 🇺🇸 Wyoming, Michigan, United States

Huron Gastroenterology PC; 🇺🇸 Ypsilanti, Michigan, United States

Doctors Hospital; 🇺🇸 Columbus, Ohio, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus; 🇺🇸 Ypsilanti, Michigan, United States

Sanford Joe Lueken Cancer Center; 🇺🇸 Bemidji, Minnesota, United States

Essentia Health - Deer River Clinic; 🇺🇸 Deer River, Minnesota, United States

Essentia Health Cancer Center; 🇺🇸 Duluth, Minnesota, United States

Essentia Health Hibbing Clinic; 🇺🇸 Hibbing, Minnesota, United States

Essentia Health Sandstone; 🇺🇸 Sandstone, Minnesota, United States

Essentia Health Virginia Clinic; 🇺🇸 Virginia, Minnesota, United States

Siteman Cancer Center at West County Hospital; 🇺🇸 Creve Coeur, Missouri, United States

Saint Francis Medical Center; 🇺🇸 Cape Girardeau, Missouri, United States

Parkland Health Center - Farmington; 🇺🇸 Farmington, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center-South County; 🇺🇸 Saint Louis, Missouri, United States

Missouri Baptist Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Christian Hospital; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital; 🇺🇸 Saint Peters, Missouri, United States

Sainte Genevieve County Memorial Hospital; 🇺🇸 Sainte Genevieve, Missouri, United States

Missouri Baptist Sullivan Hospital; 🇺🇸 Sullivan, Missouri, United States

BJC Outpatient Center at Sunset Hills; 🇺🇸 Sunset Hills, Missouri, United States

Community Hospital of Anaconda; 🇺🇸 Anaconda, Montana, United States

Billings Clinic Cancer Center; 🇺🇸 Billings, Montana, United States

Bozeman Health Deaconess Hospital; 🇺🇸 Bozeman, Montana, United States

Benefis Sletten Cancer Institute; 🇺🇸 Great Falls, Montana, United States

Logan Health Medical Center; 🇺🇸 Kalispell, Montana, United States

Community Medical Center; 🇺🇸 Missoula, Montana, United States

OptumCare Cancer Care at Seven Hills; 🇺🇸 Henderson, Nevada, United States

OptumCare Cancer Care at Charleston; 🇺🇸 Las Vegas, Nevada, United States

OptumCare Cancer Care at Fort Apache; 🇺🇸 Las Vegas, Nevada, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Mount Sinai Hospital; 🇺🇸 New York, New York, United States

Upstate Cancer Center at Oswego; 🇺🇸 Oswego, New York, United States

State University of New York Upstate Medical University; 🇺🇸 Syracuse, New York, United States

Upstate Cancer Center at Verona; 🇺🇸 Verona, New York, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Sanford Bismarck Medical Center; 🇺🇸 Bismarck, North Dakota, United States

Sanford Broadway Medical Center; 🇺🇸 Fargo, North Dakota, United States

Sanford Roger Maris Cancer Center; 🇺🇸 Fargo, North Dakota, United States

Miami Valley Hospital South; 🇺🇸 Centerville, Ohio, United States

Good Samaritan Hospital - Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Columbus Oncology and Hematology Associates Inc; 🇺🇸 Columbus, Ohio, United States

Riverside Methodist Hospital; 🇺🇸 Columbus, Ohio, United States

Grant Medical Center; 🇺🇸 Columbus, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

Premier Blood and Cancer Center; 🇺🇸 Dayton, Ohio, United States

Dayton Physician LLC - Englewood; 🇺🇸 Dayton, Ohio, United States

Miami Valley Hospital North; 🇺🇸 Dayton, Ohio, United States

Delaware Health Center-Grady Cancer Center; 🇺🇸 Delaware, Ohio, United States

Grady Memorial Hospital; 🇺🇸 Delaware, Ohio, United States

Columbus Oncology and Hematology Associates; 🇺🇸 Dublin, Ohio, United States

Dublin Methodist Hospital; 🇺🇸 Dublin, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital; 🇺🇸 Franklin, Ohio, United States

Miami Valley Cancer Care and Infusion; 🇺🇸 Greenville, Ohio, United States

Kettering Medical Center; 🇺🇸 Kettering, Ohio, United States

OhioHealth Mansfield Hospital; 🇺🇸 Mansfield, Ohio, United States

OhioHealth Marion General Hospital; 🇺🇸 Marion, Ohio, United States

Upper Valley Medical Center; 🇺🇸 Troy, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Providence Newberg Medical Center; 🇺🇸 Newberg, Oregon, United States

Saint Alphonsus Cancer Care Center-Ontario; 🇺🇸 Ontario, Oregon, United States

Providence Willamette Falls Medical Center; 🇺🇸 Oregon City, Oregon, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Providence Saint Vincent Medical Center; 🇺🇸 Portland, Oregon, United States

UPMC Altoona; 🇺🇸 Altoona, Pennsylvania, United States

Bryn Mawr Hospital; 🇺🇸 Bryn Mawr, Pennsylvania, United States

UPMC Hillman Cancer Center Erie; 🇺🇸 Erie, Pennsylvania, United States

UPMC Cancer Centers - Arnold Palmer Pavilion; 🇺🇸 Greensburg, Pennsylvania, United States

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion; 🇺🇸 Mechanicsburg, Pennsylvania, United States

Riddle Memorial Hospital; 🇺🇸 Media, Pennsylvania, United States

UPMC Hillman Cancer Center - Monroeville; 🇺🇸 Monroeville, Pennsylvania, United States

Paoli Memorial Hospital; 🇺🇸 Paoli, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI); 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Passavant Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Lankenau Medical Center; 🇺🇸 Wynnewood, Pennsylvania, United States

Women and Infants Hospital; 🇺🇸 Providence, Rhode Island, United States

Prisma Health Cancer Institute - Spartanburg; 🇺🇸 Boiling Springs, South Carolina, United States

Prisma Health Cancer Institute - Easley; 🇺🇸 Easley, South Carolina, United States

Prisma Health Cancer Institute - Butternut; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Faris; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Eastside; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Greer; 🇺🇸 Greer, South Carolina, United States

Prisma Health Cancer Institute - Seneca; 🇺🇸 Seneca, South Carolina, United States

Sanford Cancer Center Oncology Clinic; 🇺🇸 Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Hendrick Medical Center; 🇺🇸 Abilene, Texas, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Methodist Willowbrook Hospital; 🇺🇸 Houston, Texas, United States

Houston Methodist West Hospital; 🇺🇸 Houston, Texas, United States

Houston Methodist Saint John Hospital; 🇺🇸 Nassau Bay, Texas, United States

Houston Methodist Sugar Land Hospital; 🇺🇸 Sugar Land, Texas, United States

Houston Methodist The Woodlands Hospital; 🇺🇸 The Woodlands, Texas, United States

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

Inova Schar Cancer Institute; 🇺🇸 Fairfax, Virginia, United States

Inova Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

Swedish Cancer Institute-Edmonds; 🇺🇸 Edmonds, Washington, United States

Swedish Cancer Institute-Issaquah; 🇺🇸 Issaquah, Washington, United States

Swedish Medical Center-First Hill; 🇺🇸 Seattle, Washington, United States

West Virginia University Healthcare; 🇺🇸 Morgantown, West Virginia, United States

ThedaCare Regional Cancer Center; 🇺🇸 Appleton, Wisconsin, United States

Duluth Clinic Ashland; 🇺🇸 Ashland, Wisconsin, United States

Aurora Cancer Care-Southern Lakes VLCC; 🇺🇸 Burlington, Wisconsin, United States

Marshfield Medical Center-EC Cancer Center; 🇺🇸 Eau Claire, Wisconsin, United States

Aurora Saint Luke's South Shore; 🇺🇸 Cudahy, Wisconsin, United States

Aurora Health Care Germantown Health Center; 🇺🇸 Germantown, Wisconsin, United States

Aurora Cancer Care-Grafton; 🇺🇸 Grafton, Wisconsin, United States

Saint Vincent Hospital Cancer Center Green Bay; 🇺🇸 Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Saint Mary's; 🇺🇸 Green Bay, Wisconsin, United States

Aurora BayCare Medical Center; 🇺🇸 Green Bay, Wisconsin, United States

Mercyhealth Hospital and Cancer Center - Janesville; 🇺🇸 Janesville, Wisconsin, United States

Aurora Cancer Care-Kenosha South; 🇺🇸 Kenosha, Wisconsin, United States

Gundersen Lutheran Medical Center; 🇺🇸 La Crosse, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center; 🇺🇸 Madison, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - University Hospital; 🇺🇸 Madison, Wisconsin, United States

Aurora Bay Area Medical Group-Marinette; 🇺🇸 Marinette, Wisconsin, United States

Marshfield Medical Center-Marshfield; 🇺🇸 Marshfield, Wisconsin, United States

Aurora Cancer Care-Milwaukee; 🇺🇸 Milwaukee, Wisconsin, United States

Aurora Saint Luke's Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

Aurora Sinai Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

Marshfield Medical Center - Minocqua; 🇺🇸 Minocqua, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Oconto Falls; 🇺🇸 Oconto Falls, Wisconsin, United States

Vince Lombardi Cancer Clinic - Oshkosh; 🇺🇸 Oshkosh, Wisconsin, United States

Aurora Cancer Care-Racine; 🇺🇸 Racine, Wisconsin, United States

Marshfield Medical Center-Rice Lake; 🇺🇸 Rice Lake, Wisconsin, United States

Vince Lombardi Cancer Clinic-Sheboygan; 🇺🇸 Sheboygan, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay; 🇺🇸 Sturgeon Bay, Wisconsin, United States

Aurora Medical Center in Summit; 🇺🇸 Summit, Wisconsin, United States

Vince Lombardi Cancer Clinic-Two Rivers; 🇺🇸 Two Rivers, Wisconsin, United States

Aurora Cancer Care-Milwaukee West; 🇺🇸 Wauwatosa, Wisconsin, United States

Aurora West Allis Medical Center; 🇺🇸 West Allis, Wisconsin, United States

Marshfield Medical Center - Weston; 🇺🇸 Weston, Wisconsin, United States

Centro Comprensivo de Cancer de UPR; 🇵🇷 San Juan, Puerto Rico