XmAb®20717 (Vudalimab) Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer
- Conditions
- Metastatic Castration-Resistant Prostate Cancer
- Interventions
- Combination Product: vudalimab + cabazitaxel or docetaxelBiological: vudalimab monotherapyCombination Product: vudalimab + carboplatin + cabazitaxelCombination Product: vudalimab + olaparibCombination Product: vudalimab + docetaxel
- Registration Number
- NCT05005728
- Lead Sponsor
- Xencor, Inc.
- Brief Summary
This Phase 2 study will investigate the safety and clinical activity of vudalimab (XmAb20717) alone or in combination with standard of care anticancer therapies in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior therapy.
- Detailed Description
Detailed Description:
This is a Phase 2, open-label, multiple-dose, multiple-arm, parallel assignment study in patients with mCRPC who have progressed on prior therapy. It will enroll subjects into 1 of 5 molecularly defined cohorts based on the results of acceptable, documented prior diagnostic testing:
* Cohort A: Aggressive variant prostate cancer (AVPCa)
* Cohort B: Homologous recombination deficient (HRD)/cyclin-dependent kinase 12 (CDK12) biallelic loss tumors that have progressed on poly-adenosine diphosphate ribose polymerase inhibitors (HRD/CDK12 PARP Progressors) - Closed to Enrollment
* Cohort C: HRD/CDK12 biallelic loss tumors, naive to PARP inhibitors (HRD/CDK12 PARP Naïve) - Closed to Enrollment
* Cohort D: Microsatellite instability-high (MSI-H) or mismatch repair deficient (MMRD), or tumor mutational burden-high (TMB-H) tumors - Closed to Enrollment
* Cohort E: No Targetable Mutations
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 72
-
Able to provide written informed consent
-
Adult (age ≥ 18 years)
-
Histologically confirmed diagnosis of carcinoma of the prostate
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Documented progressive mCRPC based on at least one of the following criteria:
- PSA progression, defined as at least 2 rises in PSA with a minimum of a 1-week interval
- Soft-tissue progression per RECIST 1.1
- Progression of bone disease (evaluable disease) or 2 or more new bone lesions by bone scan
-
Prostate cancer must have progressed following treatment including at least 1 androgen receptor signaling inhibitor (ARSI) agent
-
Subjects who did not have a surgical orchiectomy must be on androgen suppression treatment (eg, luteinizing hormone-releasing hormone agonist) with castrate level of testosterone (≤ 50 ng/dL) and be willing to continue the treatment throughout the study
-
Prior targeted or whole exome sequencing panel performed by CLIA-certified laboratory documenting:
- Cohort A (AVPCa) - Aggressive variant prostate cancer
- Cohort B or C (HRD) - Homologous recombination deficient (HRD) tumor
- Cohort D (MSI-H/MMRD) - Microsatellite instability-high (MSI-H) or mismatch repair deficient (MMRD) tumors (MSI-H/MMRD) or TMB-H (≥ 10 mut/Mb)
- Cohort E (No Targetable Mutations)
NOTE: Cohorts B, C, and D are no longer open for enrollment
- Evaluable disease according to PCWG3 criteria
- Adequate archival metastatic tumor tissue or agree to undergo a biopsy of at least 1 metastatic site (fresh biopsy of primary prostate is only allowed if there is clear local disease and no other measurable disease site or biopsiable bone lesion)
- ECOG performance status of 0 or 1
- Able and willing to complete the study according to the study schedule
-
Currently receiving anticancer therapies other than androgen deprivation therapy
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Prior treatment with docetaxel (Cohort E only)
-
Treatment with any other anticancer therapy within 2 weeks of the start of study drug (ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
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Disease progression on prior treatment with cabazitaxel plus carboplatin (applicable to subjects eligible for Cohort A) or cabazitaxel alone (applicable to subjects eligible for Cohort E)
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Prior treatment with any cytotoxic T-lymphocyte-associated protein (CTLA4), PD1, PDL1, or programmed cell death ligand 2 (PDL2) directed immunotherapy, except subjects in Cohort D, who will have had prior FDA-approved checkpoint inhibitor therapy
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Failure to recover from any toxicity related to previous anticancer treatment to ≤ Grade 2
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Have known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, ie, are without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), are clinically stable, and are without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
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Platelet count < 100 × 109/L
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Hemoglobin level ≤ 9.0 g/dL
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Absolute neutrophil count ≤ 1.7 × 109 for subjects who will receive cabazitaxel; < 1.0 × 109/L for all others
-
Aspartate aminotransferase at screening > 3 × upper limit of normal (ULN) for subjects without known liver involvement by tumor or > 5 × ULN for subjects with known liver involvement by tumor
-
Alanine aminotransferase at screening > 3 × ULN for subjects without known liver involvement by tumor or > 5 × ULN for subjects with known liver involvement by tumor
-
Bilirubin ≥ 1.5 × ULN (unless prior diagnosis and documentation of ongoing hemolysis or Gilbert's syndrome has been made)
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Estimated creatinine clearance < 50 mL/minute calculated by the Cockcroft Gault or Modification of Diet in Renal Disease formulas
-
Active known or suspected autoimmune disease (except vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs)
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Have any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug (except inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response). Subjects who are currently taking prednisone from a previous prostate cancer therapy will be permitted to enroll in the study.
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Receipt of an organ allograft
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Known history of left ventricular ejection fraction ≤ 40%
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History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease other than their primary malignancy that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study evaluations, procedures, or completion
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Evidence of any serious bacterial, viral, parasitic, or systemic fungal infections within the 30 days prior to the first dose of study drug
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Receipt of a live-virus vaccine within 30 days prior to the first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted)
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Known human immunodeficiency virus (HIV) positive subject with CD4+ T-cell (CD4+) counts < 350 cells/μL, or an HIV viral load greater than 400 copies/mL, or a history of an AIDS (acquired immunodeficiency syndrome)-defining opportunistic infection within the past 12 months, or who has not been on established antiretroviral therapy (ART) for at least 4 weeks prior to initiation of study drug dosing. (Effective ART is defined as a drug, dosage, and schedule associated with reduction and control of the viral load.) (HIV positive subjects who do not meet any of these exclusion criteria are eligible)
-
Positive test for hepatitis C RNA (a subject who is hepatitis C virus [HCV] antibody positive but HCV RNA negative due to documented, curative prior antiviral treatment or natural resolution is eligible)
- Positive test for HBsAg or HBcAb (a subject whose HBsAg is negative and HBcAb is positive may be enrolled if a HBV DNA test is negative and the subject is retested for HBsAg and HBV DNA every 2 months)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B - HRD/CDK12 PARP - Progressors vudalimab + cabazitaxel or docetaxel - Cohort D - MSI-H, MMRD or TMB-H vudalimab monotherapy - Cohort A - AVPCa vudalimab + carboplatin + cabazitaxel - Cohort C - HRD/CDK12 PARP Naïve vudalimab + olaparib - Cohort E - No Targetable Mutations vudalimab + docetaxel -
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (safety and tolerability of vudalimab) 8 weeks
- Secondary Outcome Measures
Name Time Method Radiographic progression-free survival (PCWG3) 8 weeks Duration of response (RECIST 1.1, as modified by PCWG3) 8 weeks Prostate-specific antigen (PSA) response 8 weeks Objective response rate (RECIST 1.1, as modified by PCWG3) 8 weeks Bone scans based on PCWG3 criteria 8 weeks
Trial Locations
- Locations (25)
Alaska Oncology and Hematology
🇺🇸Anchorage, Alaska, United States
Palo Verde Hematology Oncology
🇺🇸Glendale, Arizona, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
VA Greater Los Angeles
🇺🇸Los Angeles, California, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Rocky Mountain Cancer Centers
🇺🇸Lone Tree, Colorado, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
GU Research Network/Urology Cancer Center
🇺🇸Omaha, Nebraska, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
XCancer New Mexico Oncology Hematology Consultants, Ltd.
🇺🇸Albuquerque, New Mexico, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Columbia University
🇺🇸New York, New York, United States
Northwest Cancer Specialists
🇺🇸Tigard, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Texas Oncology-Central South
🇺🇸Weslaco, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
University of Washington/Seattle Cancer Care/Alliance
🇺🇸Seattle, Washington, United States