A Study of (Neo)Adjuvant V940 and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007)

• ClinicalTrials.gov Identifier: NCT06295809
• Recruitment Status: Recruiting
• First Posted: March 6, 2024
• Last Update Posted: April 26, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: Moderna TX
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

This is a two-part (Phase 2/Phase 3) study of V940, an individualized neoantigen therapy (INT), plus pembrolizumab in participants with locally resectable advanced cutaneous squamous cell carcinoma (LA cSCC). Phase 2 has three arms V940 plus pembrolizumab given as neoadjuvant and adjuvant treatment with standard of care (SOC), standard of care (surgical resection with/without adjuvant radiation therapy (RT) only at investigator's discretion) and pembrolizumab monotherapy given as neoadjuvant and adjuvant treatment with SOC. This phase will assess the safety and efficacy of V940 in combination with pembrolizumab as neoadjuvant and adjuvant therapy in participants with resectable LA cSCC as compared to standard of care SOC only. The primary hypothesis is that V940 plus pembrolizumab with SOC is superior to SOC only with respect to event free survival (EFS) as assessed by the investigator. Phase 3 expansion will be determined by prespecified Go-No-Go decision in which 412 additional participants will be randomized to V940 plus pembrolizumab with SOC and SOC only, without changing the inclusion/exclusion criteria for the additional enrollment or study endpoints.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Squamous Cell; Skin Neoplasms	Biological: Pembrolizumab; Biological: V940; Procedure: Surgery	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1012 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: In the Phase 2 of the study design, approximately 600 participants will be randomly assigned into 3 arms in an approximate 5:5:2 ratio (250 to V940 plus pembrolizumab with SOC, 250 participants to SOC only, and 100 participants to pembrolizumab monotherapy with SOC). If the decision is made to expand the study to Phase 3, the 600 participants enrolled in Phase 2 will keep their originally assigned study intervention arms in the Phase 3 Expansion, and 412 new participants will be enrolled and randomly assigned in a 1:1 ratio to receive treatment with either V940 plus pembrolizumab with SOC or SOC only. New participants will not be randomized into the pembrolizumab monotherapy with SOC arm during the Phase 3 Expansion.
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2/3, Adaptive, Randomized, Open-label, Clinical Study to Evaluate Neoadjuvant and Adjuvant V940 (mRNA-4157) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care, and Pembrolizumab Monotherapy in Participants With Resectable Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (INTerpath-007)
• Estimated Study Start Date: May 6, 2024
• Estimated Primary Completion Date: April 30, 2029
• Estimated Study Completion Date: April 30, 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pembrolizumab plus V940 with SOC; Participants will receive V940 1 mg intramuscular (IM) injection every 3 weeks (q3w) for up to 6 weeks and pembrolizumab 400 mg intravenous (IV) infusion every 6 weeks (q6w) up to 12 weeks as neoadjuvant therapy prior to surgery; followed by V940 1 mg IM injection q3w up to 21 weeks and pembrolizumab 400 mg IV infusion q6w or until discontinuation.	Biological: Pembrolizumab; IV Infusion; Other Names: MK-3475; Keytruda®; Biological: V940; IM injection; Other Name: mRNA-4157; Procedure: Surgery; Local resection of cancerous lesions of the skin
Active Comparator: Standard of Care (SOC); Participants will receive surgical resection as per local guidelines with/without adjuvant radiation therapy (RT) at investigator's discretion.	Procedure: Surgery; Local resection of cancerous lesions of the skin
Experimental: Pembrolizumab with SOC; Participants will receive pembrolizumab 400 mg IV infusion q6w up to 12 weeks as neoadjuvant therapy prior to surgery; followed by pembrolizumab 400 mg IV infusion q6w or until discontinuation.	Biological: Pembrolizumab; IV Infusion; Other Names: MK-3475; Keytruda®; Procedure: Surgery; Local resection of cancerous lesions of the skin

Outcome Measures

Primary Outcome Measures :

1. Event Free Survival (EFS) [ Time Frame: Up to ~59 months ]
   EFS is defined as the time from randomization to any of the following events as assessed by the investigator: progression of disease that precludes surgery, or inability to undergo R0 or R1 surgical resection; disease recurrence (local, regional, or distant); new primary high-risk cSCC; death due to any cause. EFS will be presented.

Secondary Outcome Measures :

1. Overall response rate (ORR) [ Time Frame: Up to ~38 months ]
   ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR). ORR will be presented.
2. Freedom from surgery (FFS) rate [ Time Frame: Up to ~38 months ]
   FFS rate is defined as the proportion of participants with clinical CR with no residual tumor on clinical exam and imaging with the confirmation of negative biopsy. FFS rate will be presented.
3. Pathological complete response (pCR) rate [ Time Frame: Up to ~38 months ]
   pCR rate is defined as the proportion of participants who have complete absence of viable tumor in the surgical resection specimen. The pCR rate will be presented.
4. Major pathological response (mPR) rate [ Time Frame: Up to ~38 months ]
   mPR rate is defined as the proportion of participants who have ≤10% of viable tumor cells in the surgical resection specimen. The mPR rate will be presented.
5. Disease-free survival (DFS) [ Time Frame: Up to ~59 months ]
   DFS is defined as the time from surgery for participants who are free of disease (R0 or R1 resection) at completion of neoadjuvant therapy, or from negative biopsy for participants who are free from surgery to first recurrence (local, regional, or distant), new primary high-risk cSCC or death due to any cause, whichever occurs first. DFS will be presented.
6. Disease-specific survival (DSS) [ Time Frame: Up to ~59 months ]
   DSS is defined as time from randomization to death due to progression of cancer under study. DSS will be presented.
7. Overall Survival (OS) [ Time Frame: Up to ~59 months ]
   OS is defined as the time from the date of randomization to death due to any cause. The OS will be reported for all participants.
8. Percentage of participants who experience and adverse event (AE) [ Time Frame: Up to ~59 months ]
   An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.
9. Percentage of participants who discontinue study intervention due to AEs [ Time Frame: Up to ~19 months ]
   An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue intervention due to an AE will be reported.
10. Change from baseline in Global health status/QoL score (QLQ-C30 Items 29 and 30) [ Time Frame: Baseline and up to ~38 months ]
    The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" will be scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better overall health status. Per protocol, the change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.
11. Change from baseline in physical functioning score of QLQ (C30 Items 1-5) [ Time Frame: Baseline and up to ~38 months ]
    The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better level of physical functioning. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.
12. Change from baseline in Role functioning score of QLQ-C30 Items 6-7 [ Time Frame: Baseline and up to ~38 months ]
    The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a more impaired level of role functioning. Change from baseline in the role functioning (EORTC QLQ-C30 Items 6-7) combined score will be presented.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Has 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)
• Has LA Stage II-IV (M0) cSCC without distant metastases
• cSCC must be amenable to surgery (resectable) with curative intent
• 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
• 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
• 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 V940: 15 days, Pembrolizumab: 120 days, Adjuvant RT, if performed: 90 days after last exposure or is a WOCBP who is abstinent from heterosexual intercourse
• Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
• Has a life expectancy of >3 months per investigator assessment
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 14 days before randomization
• Has adequate organ function
• 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
• If there is a history of hepatitis C virus (HCV) infection, HCV viral load must be undetectable at screening
• If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

• 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
• Has distant metastatic disease (M1), visceral and/or distant nodal
• 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)
• Has received prior systemic anticancer therapy including investigational agents for cSCC before randomization
• Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• 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)
• Has received prior treatment with another cancer vaccine
• 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
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has a 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
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
• History of chronic lymphocytic leukemia (CLL)
• History of central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to either V940 or pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• 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
• Has had a myocardial infarction within 6 months of randomization
• Has a history of allogeneic tissue/solid organ transplant
• Has not adequately recovered from major surgery or have ongoing surgical complications

Contacts and Locations

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

Locations

Australia, Western Australia

One Clinical Research ( Site 3211); Recruiting

Nedlands, Western Australia, Australia, 6009

Contact: Study Coordinator +61862799466

Israel

Hadassah Medical Center ( Site 2201); Recruiting

Jerusalem, Israel, 9112001

Contact: Study Coordinator 97226777825

Rabin Medical Center ( Site 2202); Recruiting

Petah Tikva, Israel, 4941 492

Contact: Study Coordinator 97235305201

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Moderna TX

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

More Information

Additional Information:

Merck Clinical Trials Information 

Plain Language Summary 

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT06295809
• Other Study ID Numbers: V940-007; 2023-505712-37 ( Other Identifier: EU CT ); U1111-1292-3589 ( Other Identifier: UTN ); V940 ( Other Identifier: Merck )
• First Posted: March 6, 2024
• Last Update Posted: April 26, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

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

Keywords provided by Merck Sharp & Dohme LLC:

pembrolizumab

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Neoplasms, Squamous Cell; Skin Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Skin Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action