MK-2870 versus Chemotherapy in Previously Treated or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) with EGFR Mutations or Other Genomic Alterations

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

11 Nov 2025 → ongoing

Decision date (initial)

2024-02-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-503539-16-00

WHO UTN

U1111-1287-4913

ClinicalTrials.gov

NCT06074588

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Efficacy, Therapy, Safety, Pharmacokinetic

1. To compare MK-2870 to chemotherapy with respect to PFS per RECIST 1.1 as assessed by BICR in NSCLC with EGFR mutations.
2. To compare MK-2870 to chemotherapy with respect to OS in NSCLC with EGFR mutations.

Secondary objectives 8

1. To compare MK-2870 to chemotherapy with respect to PFS per RECIST 1.1 as assessed by BICR in all participants with NSCLC.
2. To compare MK-2870 to chemotherapy with respect to OS in all participants with NSCLC.
3. To compare ORR per RECIST 1.1 based on BICR of MK-2870 to chemotherapy in NSCLC with EGFR mutations.
4. To compare ORR per RECIST 1.1 based on BICR of MK-2870 to chemotherapy in all participants with NSCLC.
5. To evaluate DOR of MK-2870 versus chemotherapy in NSCLC with EGFR mutations and in all participants with NSCLC.
6. To evaluate the mean change from baseline in global health status/QoL, dyspnea, cough, and chest pain for MK-2870 versus chemotherapy in NSCLC with EGFR mutations and in all participants with NSCLC.
7. To evaluate the time to deterioration in global health status/QoL, dyspnea, cough, and chest pain for MK-2870 versus chemotherapy in NSCLC with EGFR mutations and in all participants with NSCLC.
8. To evaluate the safety and tolerability of MK-2870

Conditions and MedDRA coding

Non-small Cell Lung Cancer (NSCLC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003461-PIP01-23

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically- or cytologically-documented advanced (Stage III not eligible for resection or curative radiation) or metastatic non-squamous NSCLC with specific mutations
2. Documentation of locally assessed radiological disease progression while on or after last treatment based on Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
3. Participants with genome mutations must have received 1 or 2 prior lines of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), including a third generation TKI for participants with a T790M mutation; and 1 platinum-based therapy after progression on or after EGFR TKI
4. At least 18 years of age at the time of providing informed consent
5. Measurable disease per RECIST 1.1 as assessed by the local site investigator
6. Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
7. Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline
8. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization
9. HIV-infected participants must have well controlled HIV on ART
10. Have an ECOG performance status of 0 or 1 within 3 days before randomization

Exclusion criteria 20

1. Has predominantly squamous cell histology NSCLC
2. Has mixed tumor(s) with small cell elements
3. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
4. Has Grade ≥2 peripheral neuropathy
5. Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
6. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
7. Has an EGFR T790M mutation and has not received a third generation EGFR TKI (eg, osimertinib)
8. Received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) before randomization
9. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
10. Completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
11. Received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention
12. Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC)
13. Received prior treatment with a topoisomerase I-containing ADC
14. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
15. Known additional malignancy that is progressing or has required active treatment within the past 3 years
16. Active infection requiring systemic therapy
17. History of noninfectious pneumonitis/ILD that required steroids or has current pneumonitis/ILD
18. Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable, radiologically stable for at least 4 weeks and do not require glucocorticoids for at least 14 days prior to randomization.
19. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
20. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression-free Survival (PFS) of Participants with NSCLC with Epidermal Growth Factor Receptor (EGFR) mutations
2. Overall Survival (OS) of Participants with NSCLC with EGFR mutations

Secondary endpoints 15

1. PFS of All Participants with NSCLC
2. OS of All Participants with NSCLC
3. Objective Response Rate (ORR) of Participants with NSCLC with EGFR mutations
4. ORR of All Participants with NSCLC
5. Duration of Response (DOR) of All Participants with NSCLC
6. Change in Score from Baseline in Global Health Status/QoL Score (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) items 29 and 30)
7. Change in Score from Baseline in Dyspnea score (EORTC QLQ-C30 item 8)
8. Change in Score from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) item 31)
9. Change in Score from Baseline in Chest pain (EORTC QLQ-LC13 item 40)
10. Time to Deterioration from Baseline in Global Health Status/QoL Score (EORTS QLQ-C30 items 29 and 30)
11. Time to Deterioration from Baseline in Dyspnea score (EORTC QLQ-C30 item 8)
12. Time to Deterioration from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) item 31)
13. Time to Deterioration from Baseline in Chest pain (EORTC QLQ-LC13 item 40)
14. Number of Participants Who Experience One or More Adverse Events (AEs)
15. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

Investigational products

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

Test 1

Comparator 2

Auxiliary 5

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

Mark Shamoun

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Mark Shamoun

Third parties 7

Locations

7 EU/EEA countries · 41 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

Temporary halts 7 · Art. 38 CTR

Results and documents

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

Documents 84 files

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

Application history

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