A Trial To Find Out If Vidutolimod Together With Cemiplimab Is Safe And If It Works In Adult Participants With Advanced Cancer Or Metastatic Cancer
- Conditions
- Merkel Cell CarcinomaCutaneous Squamous Cell CarcinomaBasal Cell CarcinomaTriple Negative Breast CancerNon-Small Cell Lung CancerOropharynx Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT04916002
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The goal of this study is to learn if giving cemiplimab and vidutolimod together could be effective in treating advanced cancer. The main questions it aims to answer are:
* How many participants' cancers respond to vidutolimod together with cemiplimab?
* Is vidutolimod together with cemiplimab safe and well-tolerated?
* How well does vidutolimod together with cemiplimab treat participants' cancer?
Participants will receive trial treatment for up to 2 years. 30 days after stopping treatment, participants will have a follow-up visit. After that visit, the trial staff will continue to follow up with participants about every 3 months, until the trial ends.
- Detailed Description
Former Sponsor Checkmate Pharmaceuticals Note: Early termination planned on 31Oct2024 due to study drug supply
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 77
Participants enrolled in the study must meet all of the following inclusion criteria to be eligible.
- Histopathologically-confirmed diagnosis of cancer, as defined by the protocol.
- Measurable disease, as defined by RECIST v1.1 and as defined in the protocol. Note: CSCC, MCC and BCC subjects without radiographically measurable disease are not excluded if there is at least 1 lesion ≥ 10 mm in at east 1 dimension documented by color photography.
- Adequate organ function based on most recent laboratory values within 3 weeks before first dose of study treatment on Week 1 Day 1 (W1D1), as defined in the protocol.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 at Screening.
Key
Participants presenting with any of the following will not qualify for entry into the study:
- Received radiation therapy (or other non-systemic therapy) within 2 weeks before first dose of study treatment on W1D1. Participants should have recovered (i.e. Grade ≤ 1 or at baseline) from radiation-related toxicities.
- Had major surgeries (including complete oncologic resection) within last 4 weeks prior to enrollment, and/or have not recovered adequately from the toxicities and/or complications from the intervention. Minor surgeries (including routine resections of early stage CSCCs and BCCs that may be due to field cancerization) require a 7-day washout.
- Received systemic pharmacologic doses of corticosteroids > 10 mg/day prednisone within 15 days before first dose of study treatment on W1D1, as defined in the protocol.
- History of immune-mediated AE leading to permanent discontinuation due to prior PD-1-blocking antibody.
- Not fully recovered from AEs due to prior treatment (to Grade 1 or less, per Common Terminology Criteria for Adverse Events (CTCAE), with the exception of persistent vitiligo, alopecia, hypothyroidism, diabetes mellitus, and adrenal and/or pituitary insufficiency.
- Active pneumonitis or history of noninfectious pneumonitis that required steroids.
- Severe uncontrolled medical disease within 12 months of screening, including but not limited to poorly controlled hypertension, unstable angina, myocardial infarction, congestive heart failure (New York Heart Association Class II or greater), pericarditis, cerebrovascular accident, or implanted or continuous use of a pacemaker or defibrillator, or emphysema with FEV1 ≤ 50% predicted.
- Known history of immunodeficiency.
- Known additional malignancy that is progressing or required active treatment within the past 3 years, as defined in the protocol.
- Active autoimmune disease that required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment.
- Untreated, symptomatic, or enlarging central nervous system metastases or carcinomatous meningitis (including leptomeningeal metastases from solid tumors).
NOTE: Other protocol defined Inclusion/Exclusion Criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vidutolimod and cemiplimab for cutaneous squamous cell carcinoma (CSCC) (A1) cemiplimab Participants who have not received prior systemic therapy for metastatic or locally and/or regionally advanced unresectable CSCC and who are not eligible for curative radiation will receive vidutolimod intratumoral(ly) (IT) and cemiplimab intravenous (IV) according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for CSCC (A2) cemiplimab Participants who have progressed while receiving a programmed cell death protein 1 (PD-1)-blocking antibody or within 12 weeks of discontinuation of PD-1 blocking antibody for metastatic or locally and/or regionally advanced unresectable CSCC, will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for non-small cell lung cancer (NSCLC) (E) cemiplimab Participants with advanced NSCLC (locally advanced who are not candidates for surgical resection or definitive chemoradiation or metastatic) whose tumors have high PD-L1 expression \[tumor proportion score (TPS) ≥50%\] based on a prior PD-L1 result as determined by College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) (or equivalently licensed) lab, with no epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or ros oncogene 1 (ROS1) aberrations, and who have not received prior anti-PD-1/PD-L1 therapy and are amenable to IT therapy and do not wish to receive chemotherapy. Note: this cohort is not conducted in Europe Vidutolimod and cemiplimab for Merkel cell carcinoma (MCC) (B1) cemiplimab Participants who have not received prior systemic therapy for metastatic or locally and/or regionally advanced unresectable MCC will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for MCC (B2) cemiplimab Participants who have progressed while receiving a PD-1-blocking antibody or within 12 weeks of discontinuation of the PD-1 blocking antibody, will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for triple negative breast cancer (TNBC) (C1) vidutolimod Participants who have not received prior therapy with immune checkpoint inhibitors (iCPIs) and who must have previously received treatment with sacituzumab govitecan (all advanced or metastatic TNBC participants), with trastuzumab deruxtecan \[human epidermal growth factor receptor 2 (HER2)-low participants\] and with adenosine diphosphate ribose polymerase (PARP) inhibitor \[for BReast CAncer gene (BRCA)\] for TNBC will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for TNBC (C2) cemiplimab Participants who have previously received treatment with sacituzumab govitecan (all advanced or metastatic TNBC participants), with trastuzumab deruxtecan (HER2-low participants) and with PARP inhibitor (for BRCA) and who have progressed while receiving a PD-1-blocking antibody or within 12 weeks of discontinuation of a PD-1 blocking antibody for advanced or metastatic TNBC, will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for triple negative breast cancer (TNBC) (C1) cemiplimab Participants who have not received prior therapy with immune checkpoint inhibitors (iCPIs) and who must have previously received treatment with sacituzumab govitecan (all advanced or metastatic TNBC participants), with trastuzumab deruxtecan \[human epidermal growth factor receptor 2 (HER2)-low participants\] and with adenosine diphosphate ribose polymerase (PARP) inhibitor \[for BReast CAncer gene (BRCA)\] for TNBC will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for basal cell carcinoma (BCC) (D) cemiplimab Participants who have not received prior hedgehog pathway inhibitor therapy, or prior anti-PD-1/programmed cell death ligand 1 (PD-L1) therapy and who do not wish to receive or who are not candidates for a hedgehog inhibitor, for metastatic or locally and/or regionally advanced unresectable BCC and will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for recurrent/metastatic Oropharynx Squamous Cell Carcinoma (OPSCC) (F) cemiplimab Participants with PD-L1 combined positive score (CPS) ≥ 1, based on a prior PD-L1 result and human papillomavirus (HPV)-positive disease based on a prior result, who have not received prior systemic therapy for recurrent/metastatic disease. Participants will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for cutaneous squamous cell carcinoma (CSCC) (A1) vidutolimod Participants who have not received prior systemic therapy for metastatic or locally and/or regionally advanced unresectable CSCC and who are not eligible for curative radiation will receive vidutolimod intratumoral(ly) (IT) and cemiplimab intravenous (IV) according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for CSCC (A2) vidutolimod Participants who have progressed while receiving a programmed cell death protein 1 (PD-1)-blocking antibody or within 12 weeks of discontinuation of PD-1 blocking antibody for metastatic or locally and/or regionally advanced unresectable CSCC, will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for Merkel cell carcinoma (MCC) (B1) vidutolimod Participants who have not received prior systemic therapy for metastatic or locally and/or regionally advanced unresectable MCC will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for MCC (B2) vidutolimod Participants who have progressed while receiving a PD-1-blocking antibody or within 12 weeks of discontinuation of the PD-1 blocking antibody, will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for TNBC (C2) vidutolimod Participants who have previously received treatment with sacituzumab govitecan (all advanced or metastatic TNBC participants), with trastuzumab deruxtecan (HER2-low participants) and with PARP inhibitor (for BRCA) and who have progressed while receiving a PD-1-blocking antibody or within 12 weeks of discontinuation of a PD-1 blocking antibody for advanced or metastatic TNBC, will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for basal cell carcinoma (BCC) (D) vidutolimod Participants who have not received prior hedgehog pathway inhibitor therapy, or prior anti-PD-1/programmed cell death ligand 1 (PD-L1) therapy and who do not wish to receive or who are not candidates for a hedgehog inhibitor, for metastatic or locally and/or regionally advanced unresectable BCC and will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached. Vidutolimod and cemiplimab for non-small cell lung cancer (NSCLC) (E) vidutolimod Participants with advanced NSCLC (locally advanced who are not candidates for surgical resection or definitive chemoradiation or metastatic) whose tumors have high PD-L1 expression \[tumor proportion score (TPS) ≥50%\] based on a prior PD-L1 result as determined by College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) (or equivalently licensed) lab, with no epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or ros oncogene 1 (ROS1) aberrations, and who have not received prior anti-PD-1/PD-L1 therapy and are amenable to IT therapy and do not wish to receive chemotherapy. Note: this cohort is not conducted in Europe Vidutolimod and cemiplimab for recurrent/metastatic Oropharynx Squamous Cell Carcinoma (OPSCC) (F) vidutolimod Participants with PD-L1 combined positive score (CPS) ≥ 1, based on a prior PD-L1 result and human papillomavirus (HPV)-positive disease based on a prior result, who have not received prior systemic therapy for recurrent/metastatic disease. Participants will receive vidutolimod IT and cemiplimab IV according to the treatment schedule until a reason for treatment discontinuation is reached.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) with vidutolimod in combination with cemiplimab in study participants with metastatic or advanced/unresectable CSCC, MCC, BCC, NSCLC,TNBC or OPSCC Up to 42 Months CSCC is defined as cutaneous squamous cell carcinoma, MCC is defined as Merkel cell carcinoma, BCC is defined as Basal cell carcinoma, NSCLC is defined as Non-small cell lung cancer, TNBC is defined as triple negative breast cancer and OPSCC is defined as oropharyngeal squamous cell carcinoma. ORR is further defined as the proportion of participants with a confirmed objective response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1.)
- Secondary Outcome Measures
Name Time Method Safety and tolerability of vidutolimod administered by IT injection in combination with cemiplimab in the study participants Up to 42 Months Safety and tolerability is defined as the presence of Adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation or death, and severity of AEs as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)
Efficacy of vidutolimod in combination with cemiplimab in the study participants Up to 42 Months Efficacy is measured by: Duration of response (DOR), defined as the time from date of first documented response (CR or PR) to date of documented progressive disease (PD), based on RECIST v1.1 Response in injected and noninjected target lesions per RECIST v1.1. Progression-free survival (PFS), defined as the time from date of first dose of study treatment to date of documented PD based on RECIST v1.1 or death, whichever occurs first. Overall survival (OS), defined as the time from date of first dose of study treatment to date of death
Trial Locations
- Locations (24)
University of California
🇺🇸Los Angeles, California, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
St. Vincent's Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Peter MacCallum Cancer Centre (PMCC) and The Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Utah Huntsman Cancer Center
🇺🇸Salt Lake City, Utah, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
VA Maryland Health Care System
🇺🇸Baltimore, Maryland, United States
Dartmouth Clinical Trial Office
🇺🇸Lebanon, New Hampshire, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
City of Hope
🇺🇸Duarte, California, United States
GenesisCare USA
🇺🇸Jacksonville, Florida, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia