Clinical trial of MK-7684A plus chemotherapy compared to pembrolizumab plus chemotherapy for metastatic non-small cell lung cancer

Phase 1

• Conditions: First-line treatment of metastatic NSCLC; MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-004564-94-ES
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-12-07
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

1. Has a histologically or cytologically confirmed diagnosis of Stage IV (T any, N any, M1a, M1b, M1c - AJCC eighth Edition) squamous or nonsquamous NSCLC
2. Has measurable disease based on RECIST 1.1, as determined by the local site assessment
3. Has provided tumor tissue (post diagnosis of metastatic disease is preferred) for determination of PD-L1 status before randomization
4. Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of the absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], AND absence of ALK and ROS1 gene rearrangements)
5. Has not received prior systemic treatment for metastatic NSCLC
6. Is male or female, from =18 years of age inclusive, at the time of signing the informed consent
7. Has an ECOG PS of 0 or 1 assessed within 7 days before randomization
8. Has a life expectancy of at least 3 months
9. If male, agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows:
• Chemotherapy: at least 95 days from the last dose
• Refrain from donating sperm
PLUS either:
• Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent
OR
• Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview as detailed below:
- Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
- Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed
10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Not a WOCBP
OR
• Is a WOCBP and:
- Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
? MK-7684A/pembrolizumab: 120 days
? Chemotherapy: 180 days
- The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent tha

Exclusion Criteria

1. Known additional malignancy that is progressing or has required active treatment within the past 3 years
2. Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention. Participants with asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may participate
3. Severe hypersensitivity (=Grade 3) to MK-7684, MK-7684A, pembrolizumab, chemotherapy components, and/or any of its excipients
4. 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 before the first dose of study medication
5. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
6. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
7. Active infection requiring systemic therapy
8. Known history of HIV infection. No HIV testing is required unless mandated by local health authority
9. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
10. History or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
11. Known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
12. Received prior therapy with an anti-TIGIT, anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
13. Received prior systemic anticancer therapy for metastatic disease
14. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention
15. Received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis
16. Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention
17. Received a live or live attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
18. Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose =1.3 g/day, for a 5-day period (8-day period for long-acting agents, such as piroxicam)
19. Is unable or unwilling to take folic acid or vitamin

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified