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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Replimune Group Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Jan 2021 → 15 Jan 2026

Decision date (initial)

2024-12-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512652-38-00

EudraCT number

2018-003964-30

ClinicalTrials.gov

NCT04050436

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of this study is to estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with locally advanced or nodal or distant metastatic cutaneous squamous cell carcinoma (CSCC), as assessed by overall response rate (ORR) and complete response rate (CRR) according to blinded independent review.

Secondary objectives 12

1. To estimate the treatment effect on progression-free survival (PFS) according to blinded independent review
2. To estimate ORR/CRR (see Appendix 1 and Appendix 2) according to investigator review
3. To estimate ORR/CRR for patients with metastatic (nodal or distant) CSCC according to investigator and blinded independent review
4. To estimate ORR/CRR for patients with locally advanced CSCC according to investigator and blinded independent review
5. To estimate ORR/CRR for patients having previously received systemic CSCC-directed therapy according to investigator and blinded independent review
6. To estimate ORR/CRR for patients not having previously received systemic CSCC-directed therapy according to investigator and blinded independent review
7. To estimate the duration of response (DOR) according to investigator and blinded independent review
8. To estimate progression-free survival (PFS) according to investigator review
9. To estimate overall survival (OS)
10. To estimate 3 year survival
11. To assess the effects of cemiplimab and cemiplimab combined with RP1 on the changes in scores of patient-reported outcomes on quality of life using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
12. To assess the safety and tolerability of cemiplimab alone and combined with RP1

Conditions and MedDRA coding

Cutaneous Squamous Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Voluntary agreement to provide written informed consent and willingness and ability to comply with protocol requirements.
2. Anticipated life expectancy > 12 weeks.
3. Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception methods for 6 months after the last dose of cemiplimab or cemiplimab and RP1 combination treatment. In addition, male patients must refrain from donating sperm during this study treatment and for up to 6 months after the last dose of cemiplimab or cemiplimab and RP1 combination treatment. For a definition of highly effective contraceptive methods and instructions of patients and partners, see Section 9.3.4.9
4. Locally advanced CSCC only (Surgery): Patients must be deemed as not appropriate candidates for curative surgery in the opinion of either a medical oncologist with experience in cutaneous malignancy management, a dermatologist, a head and neck surgeon, or a multidisciplinary disease management team, or documented to have refused surgery. See Section 4.2.1 of the protocol for definitions of acceptable contraindications for surgery.
5. Locally advanced CSCC only (Radiotherapy): Patients must be deemed as not appropriate candidates for curative radiation therapy as defined in the inclusion section of the protocol, or documented as having refused radiotherapy despite consultation. This must include either a radiation oncologist, a medical oncologist, a head and neck surgeon, a dermatologist with expertise in cutaneous malignancies, or a multidisciplinary team. See Section 4.2.1 of the protocol for definitions of acceptable contraindications for radiation therapy.
6. All patients must consent to provide archived (within 12 months [6 months preferred] of screening date) or newly obtained tumor material (either formalin-fixed, paraffin-embedded [FFPE] block or unstained slides) for central pathology review for confirmation of diagnosis of CSCC and biomarker analysis.
7. Tumor biopsies will be taken as specified in the Schedules of Events (Section 9.1).
8. Histologically confirmed diagnosis of locally advanced or metastatic (nodal or distant) CSCC by local pathology report. Metastatic (nodal or distant) disease is defined as disseminated disease distant to the initial/primary site of diagnosis. The locally recurrent disease is defined as previously treated disease (with either surgery, radiotherapy, or systemic therapy) and is not amenable to either curative surgery, radiotherapy, or concurrent chemoradiotherapy treatment.
9. At least one measurable lesion and lesion(s) that are injectable, which individually or in aggregate meet the measurable criteria. There is no minimum tumor size for injection, provided there are injectable tumors that are in aggregate ≥1 cm at baseline. Note on measurable lesions: A lesion in an area that has received prior locoregional therapy, including previous radiotherapy, is not considered measurable unless there has been demonstrated progression in the lesion since the therapy as defined by RECIST 1.1 (Appendix 1) or clinical assessment criteria (Appendix 2). Note on Metastatic (nodal or distant) CSCC: Measurable lesions are lesions ≥1.0 cm in their longest diameter (≥1.5 cm shortest diameter for lymph nodes) according to RECIST 1.1. Patients with metastatic disease that does not meet target lesion criteria by RECIST 1.1 (eg, bone only lesions, perineural disease) and with externally visible CSCC target lesion(s) may be enrolled if they have at least 1 measurable externally visible lesion ≥1.0 cm in both perpendicular diameters at baseline. Composite response criteria (Appendix 2) should be used to evaluate patients who have both externally visible target lesion(s) that are evaluable by clinical response criteria (Appendix 2) and non-measurable lesions by RECIST 1.1 (Appendix 1) that are being followed radiologically as non-target lesions. Note on locally advanced CSCC: Measurable lesions are lesions ≥1.0 cm in both perpendicular diameters that are being evaluated by clinical response criteria (Appendix 2).
10. ECOG performance status (PS) ≤1 (Appendix 4). Note: Patients with ECOG PS 2 at baseline may be allowed to enroll if PS 2 status is only related to the disease under study (ie, CSCC), and they fulfill all other eligibility criteria, and upon consultation with the medical monitor.
11. Male or female ≥18 years old.
12. Hepatic function: a. Total bilirubin ≤1.5 × upper limit of normal (ULN); (if liver metastases ≤3 × ULN). Patients with Gilbert’s Disease and total bilirubin up to 3 × ULN may be eligible after communication with and approval from the medical monitor b. Transaminases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) ≤3 × ULN (or ≤5.0 × ULN, if liver metastases) c. Alkaline phosphatase (ALP) ≤2.5 x ULN (or ≤5.0 x ULN, if liver or bone metastases) Note for patients with hepatic metastases who wish to enroll: If transaminase levels (AST and/or ALT) are >3 × but ≤5 × ULN, total bilirubin must be ≤1.5 × ULN. If total bilirubin is >1.5 × but ≤3 × ULN, both transaminases (AST and ALT) must be ≤3 × ULN.
13. 7. Νεφρική λειτουργία: Κρεατινίνη ορού ≤1,5 × ΑΦΤ Ή, εάν η κρεατινίνη ορού > 1,5 × ΑΦΤ, υπολογιζόμενη κάθαρση κρεατινίνης ≥ 30 mL/min (με Cockcroft).
14. Bone marrow function: a. Hemoglobin ≥9.0 g/dL b. Absolute neutrophil count (ANC) ≥1.5 × 109/L c. Platelet count ≥100 × 109/L
15. Prothrombin time (PT) ≤1.5 × ULN (or international normalized ratio [INR] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 × ULN. See additional criteria for patients on chronic anticoagulation in the inclusion criteria section of the protocol.

Exclusion criteria 23

1. Prior treatment with an oncolytic therapy.
2. Active infection requiring systemic therapy within 14 days prior to randomization/enrollment.
3. History of interstitial lung disease (ILD)/pneumonitis within the last 5 years or a history of ILD/pneumonitis requiring treatment with systemic steroids.
4. History of myocarditis or congestive heart failure (as defined by the New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection or myocardial infarction within 6 months of randomization.
5. Grade ≥3 hypercalcemia at time of enrollme
6. Any systemic anticancer treatment (chemotherapy, targeted systemic therapy, or photodynamic therapy), investigational or standard of care, within 28 days of randomization/enrollment or planned to occur during the study period (patients receiving bisphosphonates or denosumab are not excluded). Radiation therapy within 14 days of randomization/enrollment or planned to occur during the study period. Any major surgical procedure ≤28 days before randomization. Patients must have recovered adequately from the toxicity and/or complications from prior interventions prior to randomization/enrollment.
7. Was administered a live vaccine ≤28 days before randomization. Note: Seasonal vaccines for influenza or SARS-CoV-2 are generally inactivated vaccines and are allowed (Please see Section 8.1 for additional guidance). Vaccines that are live/attenuated vaccines (such as the intranasal influenza vaccine) are not allowed
8. Patients with active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis, encephalitis, or disseminated herpes infection). Note: patients with sporadic cold sores l may be enrolled as long as no active cold sores are present at the time of randomization/enrollment. See Section 5.5 for further guidance
9. Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
10. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for ImAEs or a diagnosis of immunodeficiency disorders (such as human immunodeficiency virus [HIV] disease or organ transplantation or hematologic malignancies associated with immune suppression). Note: The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, alopecia areata or psoriasis that does not require systemic treatment.
11. Prior treatment with an agent that blocks the programmed cell death-1 (receptor) (PD-1)/PD-L1 pathway
12. Prior treatment with other immune modulating agents other than as adjuvant or neoadjuvant therapy within 3 years. Examples of immune modulating agents include therapeutic anticancer vaccines, cytokine treatments (other than granulocyte colony-stimulating factor [G-CSF] or erythropoietin), or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), PI 3-K-delta, or OX-40.
13. Untreated brain metastasis(es) that are considered active. See exclusion criteria in the protocol for exceptions for brain metastases (Section 4.2.2).
14. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to randomization/enrollment. See exclusion criteria in protocol for exceptions for corticosteroids (Section 4.2.2).
15. Patient who has acute or chronic active hepatitis B or known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C virus (defined as HCV RNA [qualitative] or HIV infection. Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated.
16. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments.
17. Patients with allergy or hypersensitivity to RP1’s or cemiplimab’s excipients must be excluded.
18. Female who has a positive serum β-hCG pregnancy (at screening within 72 hours before dosing) and urine pregnancy test (Cycle 1 Day1) or is breast feeding or planning to become pregnant.
19. Concurrent malignancy other than CSCC and/or history of malignancy other than CSCC within 3 years of date of first planned dose of cemiplimab, except for tumors with negligible risk of metastasis or death. Examples are provided in Section 4.2.2.
20. Any acute or chronic psychiatric problems or substance abuse disorders that, in the opinion of the investigator, would interfere with the patient cooperating with the requirements of the study.
21. Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the investigator, renders the patient unsuitable for participation in a clinical trial due to high safety risks and/or potential to affect interpretation of results of the study.
22. Inability to undergo any contrast-enhanced radiologic response assessment (except as outlined in the protocol eligibility exclusion section [Section 4.2.2]).
23. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization/enrollment. See exclusion criteria in the protocol for exceptions (Section 4.2.2).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The primary efficacy endpoints for this study are ORR and CRR according to blinded independent review:
2. ORR/CRR will be determined using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (RECIST 1.1) as specified in Appendix 1 for radiologically assessable lesions and clinical and composite response criteria as specified in Appendix 2 for clinically assessable lesions. Confirmatory scans should also be obtained ≥4 weeks following initial documentation of objective response or progressive disease (PD).
3. In patients suspected of achieving a complete response (CR) by clinical assessment, tumor biopsies may be used in the final determination of CR.

Secondary endpoints 12

1. The key secondary outcome measure is PFS by blinded independent review.
2. ORR/CRR by investigator review
3. ORR/CRR for patients with metastatic (nodal or distant) disease by investigator and BIRC review
4. ORR/CRR for patients with locally advanced disease by investigator and blinded independent review
5. ORR/CRR for patients having previously received systemic CSCC-directed therapy by investigator and blinded independent review
6. ORR/CRR for patients not having previously received systemic CSCC-directed therapy by investigator and blinded independent review
7. DOR by investigator and blinded independent review
8. PFS by investigator review
9. OS
10. 3-year survival
11. Change in scores of patient-reported outcomes on EORTC QLQ-C30
12. To assess the safety and tolerability of cemiplimab alone and combined with RP1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Replimune Group Inc.

Sponsor organisation

Replimune Group Inc.

Address

500 Unicorn Park Drive Floor Third

City

Woburn

Postcode

01801-3377

Country

United States

Scientific contact point

Organisation

Replimune Group Inc.

Contact name

Kari Jeschke, SVP Regulatory Affairs

Public contact point

Organisation

Replimune Group Inc.

Contact name

Kari Jeschke, SVP Regulatory Affairs

Third parties 10

Locations

6 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications