Clinical trial of V940 and pembrolizumab in people with resectable locally advanced cutaneous squamous cell carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Jun 2024 → 6 Mar 2026

Decision date (initial)

2024-05-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · Moderna

External identifiers

EU CT number

2023-505712-37-00

WHO UTN

U1111-1292-3589

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Therapy, Pharmacoeconomic, Pharmacogenomic, Safety, Efficacy

To evaluate V940 plus pembrolizumab, SOC and pembrolizumab monotherapy with respect to EFS as assessed by investigator.

Secondary objectives 7

1. To evaluate V940 plus pembrolizumab, SOC and pembrolizumab monotherapy with respect to the OR prior to surgery per RECIST 1.1 as assessed by investigator.
2. To evaluate V940 plus pembrolizumab, SOC and pembrolizumab monotherapy with respect to FFS as assessed by investigator.
3. To evaluate V940 plus pembrolizumab, SOC and pembrolizumab monotherapy with respect to pCR as assessed by BICR.
4. To evaluate V940 plus pembrolizumab, SOC and pembrolizumab monotherapy with respect to mPR as assessed by BICR.
5. To evaluate V940 plus pembrolizumab, SOC and pembrolizumab monotherapy with respect to DSS as assessed by investigator.
6. To evaluate V940 plus pembrolizumab, SOC and pembrolizumab monotherapy with respect to OS.
7. To evaluate the safety and tolerability of V940 plus pembrolizumab, SOC and pembrolizumab monotherapy.

Conditions and MedDRA coding

The participants must have a histologically confirmed diagnosis of resectable cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted).

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Has a histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted).
2. Has locally advanced (LA) Stage II-IV (M0) cSCC without distant metastases.
3. cSCC is amenable to surgery (resectable) with curative intent.
4. Has a formalin-fixed, paraffin-embedded (FFPE) tumor sample available or is able to provide one that is suitable for the Next-generation Sequencing (NGS) required for this study.
5. Is an individual of any sex/gender and at least 18 years of age.
6. For males, agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving adjuvant radiation therapy (RT), and for ≥3 months after the last dose of study intervention.
7. Is female and not pregnant/breastfeeding and at least one of the following applies during the study : is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) at least during use of intismeran autogene: 15 days, Pembrolizumab: 120 days, Adjuvant RT, if performed: 90 days after last exposure or is a WOCBP who is abstinent from heterosexual intercourse.
8. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
9. Has a life expectancy of >3 months per investigator assessment.
10. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 14 days before randomization.
11. Has adequate organ function.
12. If hepatitis B surface antigen (HBsAg) positive must have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
13. If there is a history of hepatitis C virus (HCV) infection HCV viral load must be undetectable at screening.
14. If human Immunodeficiency Virus (HIV)-infected must have well controlled HIV on antiretroviral therapy (ART).

Exclusion criteria 23

1. Has any other histologic type of skin cancer other than invasive cSCC as well as mixed histology, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, Merkel cell carcinoma (MCC), or melanoma.
2. Has distant metastatic disease (M1), visceral and/or distant nodal.
3. Has received prior therapy with an anti-programmed cell death receptor 1 (anti-PD-1), anti-programmed cell death receptor ligand 1 (anti-PD-L1), or anti-programmed cell death receptor ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte associated protein 4 (CTLA-4), OX-40, CD137).
4. Has received prior systemic anticancer therapy including investigational agents for cSCC before randomization.
5. Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
6. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
7. Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the screening blood sample (including the NGS blood sample).
8. Has received prior treatment with another cancer vaccine.
9. Has received prior radiotherapy to the index lesion (in-field lesion). Must have recovered from all radiation-related toxicities prior to randomization and not have had radiation pneumonitis.
10. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
11. Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
12. Has known additional malignancy that is progressing or has required active treatment within the past 2 years.
13. History of chronic lymphocytic leukemia (CLL).
14. History of central nervous system (CNS) metastases and/or carcinomatous meningitis.
15. Has severe hypersensitivity (≥Grade 3) to either intismeran autogene or pembrolizumab and/or any of its excipients.
16. Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
17. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
18. Has active infection requiring systemic therapy.
19. Has HIV with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
20. Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection
21. Has had a myocardial infarction within 6 months of randomization.
22. History of allogeneic tissue/solid organ transplant.
23. Has not adequately recovered from major surgery or have ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-Free Survival

Secondary endpoints 8

1. Objective Response Rate
2. Freedom From Surgery Rate
3. Pathologic Complete Response Rate
4. Major Pathologic Response Rate
5. Disease-Specific Survival
6. Overall Survival
7. Percentage of Participants Who Experience an Adverse Event (AE)
8. Percentage of Participants Who Discontinue Study Intervention Due to AEs

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jianda Yuan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jianda Yuan

Third parties 9

Locations

10 EU/EEA countries · 36 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 110 files

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

Application history

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