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

• ClinicalTrials.gov Identifier: NCT04916002
• Recruitment Status: Suspended
• First Posted: June 7, 2021
• Last Update Posted: April 5, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: June 1, 2021
• First Posted Date: June 7, 2021
• Last Update Posted Date: April 5, 2024
• Actual Study Start Date: November 30, 2021
• Estimated Primary Completion Date: July 29, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2024)

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 [ Time Frame: 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.)

Original Primary Outcome Measures (submitted: June 1, 2021)

Objective response rate (ORR) with CMP-001 in combination with a programmed cell death protein 1 (PD-1)-blocking antibody (cemiplimab-rwlc) in study subjects with metastatic or advanced/unresectable CSCC, MCC, or TNBC [ Time Frame: From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs) ]

CSCC is defined as cutaneous squamous cell carcinoma, MCC is defined as Merkel cell carcinoma, and TNBC is defined as triple negative breast cancer. ORR is further defined as the proportion of subjects 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).

Current Secondary Outcome Measures (submitted: March 30, 2023)

• Safety and tolerability of vidutolimod administered by IT injection in combination with cemiplimab in the study participants [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome Measures (submitted: June 1, 2021)

• Safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with a PD-1-blocking antibody (cemiplimab-rwlc) in the study subjects [ Time Frame: From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs) ]
  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 CMP-001 in combination with a PD-1-blocking antibody (cemiplimab-rwlc) in the study subjects [ Time Frame: From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs) ]
  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 Immune ORR, DOR, and progression-free survival (iORR, iDOR, and iPFS) based on immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) treatment response in noninjected target lesions 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Multicenter, Open-label, Phase 2 Study of Intratumoral Vidutolimod (CMP-001) in Combination With Intravenous Cemiplimab in Subjects With Selected Types of Advanced or Metastatic Cancer

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
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Merkel Cell Carcinoma
• Cutaneous Squamous Cell Carcinoma
• Basal Cell Carcinoma
• Triple Negative Breast Cancer
• Non-Small Cell Lung Cancer
• Oropharynx Squamous Cell Carcinoma

Intervention

• Drug: vidutolimod
  Participants will receive vidutolimod for up to 2 years as follows: 10 mg IT weekly for 7 doses after which vidutolimod will be administered every 3 weeks (Q3W). The first dose of vidutolimod may be administered subcutaneously (SC) or IT at the discretion of Investigator. All subsequent doses will be IT. The initial 7 doses of vidutolimod, delivered on a weekly dosing schedule, must be completed before starting the Q3W vidutolimod dosing schedule.
  Other Name: CMP-001
• Drug: cemiplimab
  Participants will receive cemiplimab for up to 2 years as follows: 350 mg IV infusion over 30 minutes at week 1 dose 1 (W1D1) and Q3W thereafter.
  Other Names:

  • Libtayo
  • REGN2810

Study Arms

• Experimental: Vidutolimod and cemiplimab for cutaneous squamous cell carcinoma (CSCC) (A1)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for CSCC (A2)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for Merkel cell carcinoma (MCC) (B1)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for MCC (B2)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for triple negative breast cancer (TNBC) (C1)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for TNBC (C2)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for basal cell carcinoma (BCC) (D)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for non-small cell lung cancer (NSCLC) (E)

  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

  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab
• Experimental: Vidutolimod and cemiplimab for recurrent/metastatic Oropharynx Squamous Cell Carcinoma (OPSCC) (F)
  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.
  Interventions:

  • Drug: vidutolimod
  • Drug: cemiplimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: February 1, 2024): 225
• Original Estimated Enrollment (submitted: June 1, 2021): 268
• Estimated Study Completion Date: July 29, 2027
• Estimated Primary Completion Date: July 29, 2027 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT04916002
• Other Study ID Numbers: CMP-001-009; 2023-507344-36-01 ( Registry Identifier: EUCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• URL: https://vivli.org/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Checkmate Pharmaceuticals
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Checkmate Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: March 2024