Pembrolizumab as adjuvant therapy for resectable high-risk LA cSCC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Mar 2019 → 21 Jan 2026

Decision date (initial)

2023-01-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-500395-57-00

EudraCT number

2018-001974-76

WHO UTN

U1111-1275-8212

ClinicalTrials.gov

NCT03833167

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Efficacy, Pharmacogenetic, Therapy

To compare the recurrence-free survival (RFS), as assessed by the investigator and confirmed by biopsy, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy.

Secondary objectives 3

1. To compare overall survival (OS) in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy.
2. To compare mean change from baseline in health-related quality of life (HRQoL) scores from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, in individuals who receive pembrolizumab with individuals who receive placebo as adjuvant therapy.
3. To determine the safety and tolerability of pembrolizumab as adjuvant therapy.

Conditions and MedDRA coding

Resectable high-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC)

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 12

1. Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another type of primary cancer or from an unknown primary cancer is not permitted)
2. Has histologically confirmed LA cSCC with ≥1 high-risk feature(s) as the primary site of malignancy
3. Has undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. For those participants with residual microscopic positive margin involvement, confirmation that additional re-excision is not possible must be provided
4. Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization
5. Has received an adequate post-op dose of RT (either hypofractionated or conventional)
6. Is disease free as assessed by the investigator with complete radiographic staging assessment ≤28 days from randomization
7. Is not pregnant or breastfeeding
8. Is not a person of childbearing potential (POCBP)
9. Has a negative pregnancy test ≤72 hours before the first dose of study intervention
10. Has provided an archival or newly-obtained tumor tissue sample adequate for Programmed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratory testing
11. Has a life expectancy of >3 months
12. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ≤10 days prior to the first dose of study intervention

Exclusion criteria 15

1. Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization
2. Has any other histologic type of skin cancer other than invasive cSCC (eg, basal cell carcinoma) that has not been definitively treated with surgery or radiation; Bowen’s disease; Merkel cell carcinoma; or melanoma
3. Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti- PD-L1, or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another co-stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
4. Has received prior systemic anticancer therapy including investigational agents for cSCC ≤4 weeks prior to before start of study intervention
5. Has not recovered from all radiation-related toxicities and has not had radiation pneumonitis
6. Has received a live vaccine ≤30 days prior to the first dose of study intervention
7. Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
8. Has known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Other exceptions may be considered with Sponsor consultation. Note: Participants with low risk early-stage prostate cancer defined as below are not excluded: Stage T1c or T2a with a Gleason score ≤6 and a prostate-specific antigen (≤10 ng/ml) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation. Early stage asymptomatic CLL without prior treatment and without any of the risk features (unmutated IGHV, lymphocytes >15,000μL, palpable lymph nodes) will be eligible for the study
9. Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
10. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
11. Has an active infection requiring systemic therapy
12. Has a known history of human immunodeficiency virus (HIV) infection
13. Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection
14. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
15. Has had an allogeneic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy

Secondary endpoints 5

1. Overall Survival (OS)
2. Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
3. Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score
4. Percentage of Participants Who Experience an Adverse Event (AE)
5. Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme Corp.

Sponsor organisation

Merck Sharp & Dohme Corp.

Address

1 Merck Drive, PO Box 100 PO Box 100

City

Whitehouse Station

Postcode

08889-3400

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme Corp.

Contact name

Jianda Yuan

Public contact point

Organisation

Merck Sharp & Dohme Corp.

Contact name

Jianda Yuan

Third parties 6

Locations

11 EU/EEA countries · 54 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 160 files

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

Application history

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