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Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer

Phase 2
Active, not recruiting
Conditions
Advanced Cutaneous Squamous Cell Carcinoma
Metastatic Cutaneous Squamous Cell Carcinoma
Cutaneous Squamous Cell Carcinoma
Interventions
Registration Number
NCT04050436
Lead Sponsor
Replimune Inc.
Brief Summary

To estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with locally advanced or metastatic CSCC, as assessed by overall response rate (ORR) and complete response rate (CRR) according to blinded independent review.

Detailed Description

RP1 is a selectively replication competent herpes simplex virus type 1(HSV-1). This is a Phase 1/2, open-label, multicenter repeat-dosing study of RP1 alone and in combination with nivolumab in patients with advanced malignancies, and contains both single agent dose escalation, dose expansion to include nivolumab, and the combination in multiple Phase 2 cohorts in individual tumor types.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
231
Inclusion Criteria
  • Histologically confirmed locally advanced or metastatic cutaneous squamous cell carcinoma
  • Patients with locally advanced disease who are not suitable candidates for surgical or radiological treatment of lesions or have refused those treatments
  • At least 1 lesion that is measurable and injectable by study criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients with ECOG PS 2 at baseline may be allowed to enroll if PS 2 status is only related to the CSCC disease under study
  • Anticipated life expectancy >12 weeks
  • All patients must consent to provide archived or newly obtained tumor material for central pathology review for confirmation of diagnosis of CSCC.

Key

Exclusion Criteria
  • Prior treatment with an oncolytic therapy
  • Patients with active significant herpetic infections or prior complications of HSV-1 infection (e.g. herpetic keratitis or encephalitis)
  • Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g. acyclovir)
  • Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
  • Prior treatment with an agent that blocks the PD-1/PD-L1 pathway.
  • Prior treatment with other immune modulating agents other than as adjuvant or neoadjuvant therapy within 3 years.
  • Untreated brain metastasis(es) that may be considered active.
  • Acute or chronic active hepatitis B or known history of hepatitis B or hepatitis C or human immunodeficiency virus (HIV) infection
  • History of ILD/pneumonitis within the last 5 years or a history of ILD/pneumonitis requiring treatment with systemic steroids.
  • Any major or surgical procedure ≤ 28 days before randomization
  • Administration of live vaccines ≤ 28 days before randomization

Note: Other protocol defined Inclusion/Exclusion criteria apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cemiplimab in combination with RP1CemiplimabCemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks
CemiplimabCemiplimabCemiplimab administered intravenously as a single therapy every 3 weeks
Cemiplimab in combination with RP1RP1Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks
Primary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) according to blinded independent reviewup to 5 years
Complete Response Rate (CRR) according to blinded independent reviewup to 5 years
Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)up to 5 years
Change in overall scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)approximately 30 months
Evaluation of the safety and tolerability of cemiplimab alone and combined with RP1 as assessed via adverse events (AEs)approximately 26 months
ORR/CRR for patients who have and have not previously received systemic CSCC-directed therapy and blinded independent reviewup to 5 years
Progression Free Survival (PFS) by blinded independent review.up to 5 years
ORR/CRR by investigator assessment and blinded independent reviewup to 5 years
3-year survival3 years
ORR/CRR for patients with metastatic or locally advanced disease according to investigator review and blinded independent reviewup to 5 years
Progression-free Survival (PFS) per investigator reviewup to 5 years
Duration of Response (DOR) per investigator review and blinded independent reviewup to 5 years

Trial Locations

Locations (56)

University of California San Diego

🇺🇸

La Jolla, California, United States

University of California Los Angeles

🇺🇸

Los Angeles, California, United States

Stanford University

🇺🇸

Stanford, California, United States

University of Colorado Cancer Center

🇺🇸

Aurora, Colorado, United States

University of Miami Health System

🇺🇸

Miami, Florida, United States

Orlando Health UF Health Cancer Center

🇺🇸

Orlando, Florida, United States

Moffitt McKinley Outpatient Center

🇺🇸

Tampa, Florida, United States

Winship Cancer Institute of Emory University

🇺🇸

Atlanta, Georgia, United States

John Theurer Cancer Center at Hackensack Univeristy Medical Center

🇺🇸

Hackensack, New Jersey, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Scroll for more (46 remaining)
University of California San Diego
🇺🇸La Jolla, California, United States

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