MK-7684A (new drug co-formulation of pembrolizumab with an anti-TIGIT) plus docetaxel works to help stop or slow down the growth of your non-small cell lung cancer (NSCLC) compared to docetaxel alone

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

15 Apr 2021 → 17 Oct 2024

Decision date (initial)

2023-03-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501252-28-00

EudraCT number

2020-004034-38

WHO UTN

U1111-1275-8661

ClinicalTrials.gov

NCT04725188

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacogenomic, Pharmacogenetic, Pharmacodynamic, Pharmacokinetic

1. To compare MK-7684A + docetaxel to normal saline placebo + docetaxel with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
2. To compare MK-7684A to normal saline placebo + docetaxel with respect to PFS per RECIST 1.1 as assessed by BICR

Secondary objectives 4

1. To evaluate Objective Response Rate (ORR) in participants treated with MK-7684A +docetaxel, MK-7684A, or normal saline placebo + docetaxel per RECIST 1.1 by BICR
2. To evaluate Overall Survival (OS) in participants treated with MK-7684A + docetaxel, MK-7684A, or normal saline placebo + docetaxel
3. To evaluate Duration of Response (DOR) per RECIST 1.1 as assessed by BICR in participants treated with MK-7684A + docetaxel, MK- 7684A, or normal saline placebo + docetaxel
4. To evaluate the safety and tolerability in participants treated with MK-7684A + docetaxel, MK-7684A, or normal saline placebo + docetaxel.

Conditions and MedDRA coding

Non Small Cell Lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
2. Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or reactive oxygen species (ROS) 1 directed therapy is not indicated as primary therapy
3. Has progressive disease (PD) on treatment with one prior anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment
4. Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease
5. Has measurable disease defined as at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI), based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
6. Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
7. Has a life expectancy of at least 3 months
8. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days prior to randomization
9. Male participants randomized to docetaxel are eligible to participant if they agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) must agree to follow contraceptive guidance as per study protocol unless confirmed to be azoospermic during the intervention period and for at least 180 days after the last dose of docetaxel
10. Female participants must be not pregnant, not breastfeeding, and not be a woman of child-bearing potential (WOCBP). A WOCBP is eligible is she agrees to either use contraception, or be abstinent from heterosexual intercourse during the intervention period and for ≥120 days after the last dose of study intervention. If a WOCBP is randomized to docetaxel, she agrees not to donate eggs and either uses contraception or be abstinent from heterosexual intercourse during the treatment period and for ≥180 days after the last dose of docetaxel
11. Has adequate organ function

Exclusion criteria 13

1. Has known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
2. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy
3. Has received docetaxel as monotherapy or in combination with other therapies
4. Has received previous treatment with another agent targeting the T-cell immunoreceptor with immunoglobulin [Ig] and immunoreceptor tyrosine-based inhibitory motif [ITIM] domains (TIGIT) pathway
5. Has received radiotherapy within 2 weeks of start of study intervention. One week washout is permitted for palliative radiation to non-CNS disease
6. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
8. Has severe hypersensitivity (≥Grade 3) to docetaxel or pembrolizumab/vibostolimab coformulation and/or any of its excipients. Has an active autoimmune disease that has required systemic treatment in past 2 years
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention
10. Has interstitial lung disease, or history of pneumonitis requiring steroids for treatment
11. Has known history of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
12. Has had an allogenic tissue/solid organ transplant
13. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment

Secondary endpoints 5

1. Objective Response (OR) per RECIST 1.1 by BICR Assessment
2. Overall Survival (OS)
3. Duration of Response (DOR) per RECIST 1.1 by BICR Assessment
4. Number of Participants Who Experienced an Adverse Event (AE)
5. Number of Participants Who Discontinued Study Treatment Due to an AE

Investigational products

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

Test 2

Placebo 1

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

Debra Kush

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Debra Kush

Third parties 7

Locations

9 EU/EEA countries · 31 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 97 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