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

Regeneron Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Cutaneous Squamous Cell Carcinoma; Oropharynx Squamous Cell Carcinoma; Triple Negative Breast Cancer; Non-Small Cell Lung Cancer; Basal Cell Carcinoma; Merkel Cell Carcinoma

Treatments: Drug: cemiplimab; Drug: vidutolimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT04916002

CMP-001-009

2023-507344-36-01 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

Former Sponsor Checkmate Pharmaceuticals Note: Early termination planned on 31Oct2024 due to study drug supply

Enrollment: 77 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Participants enrolled in the study must meet all of the following inclusion criteria to be eligible.

1. Histopathologically-confirmed diagnosis of cancer, as defined by the protocol.
2. 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.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 at Screening.

Key Exclusion Criteria:

Participants presenting with any of the following will not qualify for entry into the study:

1. 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.
2. 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.
3. 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.
4. History of immune-mediated AE leading to permanent discontinuation due to prior PD-1-blocking antibody.
5. 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.
6. Active pneumonitis or history of noninfectious pneumonitis that required steroids.
7. 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.
8. Known history of immunodeficiency.
9. Known additional malignancy that is progressing or required active treatment within the past 3 years, as defined in the protocol.
10. Active autoimmune disease that required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment.
11. 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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77 participants in 9 patient groups

Vidutolimod and cemiplimab for cutaneous squamous cell carcinoma (CSCC) (A1)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for CSCC (A2)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for Merkel cell carcinoma (MCC) (B1)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for MCC (B2)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for triple negative breast cancer (TNBC) (C1)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for TNBC (C2)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for basal cell carcinoma (BCC) (D)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for non-small cell lung cancer (NSCLC) (E)

Experimental group

Description:

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

Treatment:

Drug: vidutolimod

Drug: cemiplimab

Vidutolimod and cemiplimab for recurrent/metastatic Oropharynx Squamous Cell Carcinoma (OPSCC) (F)

Experimental group

Description:

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.

Treatment:

Drug: vidutolimod

Drug: cemiplimab