MK-1084 with Pembrolizumab in 1L Locally Advanced or Metastatic NSCLC With KRAS G12C Mutations and PD-L1 ≥50%

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

14 Nov 2024 → ongoing

Decision date (initial)

2024-09-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-507776-42-00

WHO UTN

U1111-1296-8093

ClinicalTrials.gov

NCT06345729

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacokinetic, Safety

1. To compare MK-1084 plus pembrolizumab with placebo plus pembrolizumab with respect to PFS assessed according to RECIST 1.1 by BICR

To compare MK-1084 plus pembrolizumab with placebo plus pembrolizumab with respect to OS

Secondary objectives 5

1. 1. To evaluate MK-1084 plus pembrolizumab with placebo plus pembrolizumab with respect to ORR per RECIST 1.1 as assessed by BICR
2. 2. To evaluate MK-1084 plus pembrolizumab with placebo plus pembrolizumab with respect to DOR per RECIST 1.1 as assessed by BICR
3. 3. To evaluate MK-1084 plus pembrolizumab with placebo plus pembrolizumab with respect to safety and tolerability
4. 4. To evaluate MK-1084 plus pembrolizumab with placebo plus pembrolizumab with respect to the mean change from baseline in global health status/QoL, physical functioning, role functioning, dyspnea, cough, and chest pain
5. 5. To evaluate MK-1084 plus pembrolizumab with placebo plus pembrolizumab with respect to the time to deterioration in global health status/QoL, physical functioning, role functioning, dyspnea, cough, and chest pain

Conditions and MedDRA coding

Non-small cell lung cancer

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 7

1. Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
2. Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8
3. Provides an archival tumor tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, PD-L1 status, and biomarker research
4. If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to < Grade 1 or baseline
5. If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)
6. If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
7. If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable

Exclusion criteria 16

1. Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible.
2. Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
3. Has known history of, or active, neurologic paraneoplastic syndrome
4. Has an active infection requiring systemic therapy, with exceptions
5. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
6. Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mmHg and/or any diagnosis of glaucoma, diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease
7. Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC
8. Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
9. Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis
10. Has known active central nervous system metastases and/or carcinomatous meningitis
11. Known additional malignancy that is progressing or has required active treatment within the past 3 years
12. Has active autoimmune disease that has required systemic treatment in the past 2 years
13. Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
14. Is HIV-infected and has a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
15. Has history of allogenic tissue/solid organ transplant
16. Has not fully recovered from any effects of major surgical procedure

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Progression-free survival (PFS)
2. 2. Overall survival (OS)

Secondary endpoints 16

1. 1. Objective response rate (ORR)
2. 2. Duration of response (DOR)
3. 3. Number of participants who experience one or more Adverse Events (AEs)
4. 4. Number of participants who discontinue study treatment due to an AE
5. 5. Change from baseline in global health status/quality of life (items 29 and 30) score, on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
6. 6. Change from baseline in the physical functioning (items 1-5) score, on the EORTC QLQ-C30
7. 7. Change from baseline in the role functioning (items 6-7) score, on the EORTC QLQ-C30
8. 8. Change from baseline in the dyspnea (item 8) score, on the EORTC QLQ-C30
9. 9. Change from baseline in the cough (item 31) score, on the EORTC QLQ- LC13
10. 10. Change from baseline in the chest pain (item 40) score, on the EORTC QLQ-LC13
11. 11. Time to deterioration (TTD) in global health status/quality of life (items 29 and 30) score, on the EORTC-QLQ-C30
12. 12. TTD in the physical functioning (items 1-5) score, on the EORTC-QLQ-C30
13. 13. TTD in the role functioning (items 6-7) score, on the EORTC QLQ-C30
14. 14. TTD in the dyspnea (item 8) score, on the EORTC QLQ-C30
15. 15. TTD in the cough (item 31) score, on the EORTC QLQ-Lung Cancer version (LC13)
16. 16. TTD in the chest pain (item 40) score, on the EORTC QLQ-LC13

Investigational products

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

Test 3

Placebo 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

Azadeh Namakydoust

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Azadeh Namakydoust

Third parties 7

Locations

10 EU/EEA countries · 61 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

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