Clinical trial · Interventional
Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)
A Phase 3 Study of Pembrolizumab in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Followed by Pembrolizumab and Maintenance Olaparib vs Maintenance Pemetrexed in the First-Line Treatment of Participants With Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 29, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260929-000001
Summary
Brief summary (as posted)
The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, versus (vs) pembrolizumab plus maintenance pemetrexed for the treatment of non-squamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent clinical review (BICR) and 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to overall survival (OS).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Carcinoma, Nonsquamous Non-small-cell Lung | Carcinoma | ONTOLOGY_EXACT | 0.85 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Carboplatin | Drug | Carboplatin | ALIAS |
| Cisplatin | Drug | Cisplatin | ALIAS |
| Olaparib | Drug | Olaparib | ALIAS |
| Pembrolizumab | Biological | Pembrolizumab | ALIAS |
| Pemetrexed | Drug | Pemetrexed | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib
- description
- For the Induction Phase, participants receive 4 cycles (up to \~12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg intravenous (IV) on Day 1 of each cycle (cycles 1 through 4) PLUS pemetrexed 500 mg/m\^2 IV on Day 1 of each cycle (cycles 1 through 4) PLUS platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of each cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of each cycle (Cycles 1 through 4). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. The participant can continue to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]).
- interventionNames
- Biological: Pembrolizumab
- Drug: Pemetrexed
- Drug: Carboplatin
- Drug: Cisplatin
- Drug: Olaparib
- type
- ACTIVE_COMPARATOR
- label
- Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 1. Have a histologically or cytologically confirmed diagnosis nonsquamous NSCLC. 2. Have stage IV nonsquamous NSCLC. 3. Have confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1)-directed therapy is not indicated. 4. Have measurable disease based on RECIST 1.1. 5. Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Note: Adequacy of biopsy specimen for the above analyses must be confirmed by the central laboratory before the participant can start the induction phase. Submission of another tumor specimen may be required prior to enrolling the participant, if adequate tumor tissue was not provided the first time. 6. Have a life expectancy of at least 3 months. 7. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status assessed within 7 days prior to the administration of study intervention. 8. Have not received prior systemic treatment for their advanced/metastatic NSCLC. 9. Have adequate organ function. 10. Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for 180 days afterwards. 11. Male participants must refrain from donating sperm, and female participants must refrain from donating eggs to others or freeze/store for her own use during the treatment period and for 180 days afterwards. Exclusion Criteria: 1. Has predominantly squamous cell histology NSCLC. 2. Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment. 3. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 4. Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 5. Has a known hypersensitivity to any components or excipients of cisplatin, carboplatin, pemetrexed, or olaparib. 6. Has an active autoimmune disease that has required systemic treatment in past 2 years. 7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy. 8. Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B infection, or known active hepatitis C virus infection. 9. Has interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment. 10. Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor. 11. Has received prior therapy with an agent directed to programmed cell death ligand 1 (PD-L1), anti PD-L2, or directed to a stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137). 12. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML. 13. Has completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
References
Publications (1)
- RESULTGray JE, Schenker M, Sendur MAN, Leonova V, Kowalski D, Kato T, Orlova R, Yang JC, Langleben A, Pilz A, Ungureanu A, Mak MP, De Angelis F, Aggarwal H, Zimmer Z, Zhao B, Shamoun M, Kim TM. The Phase 3 KEYLYNK-006 Study of Pembrolizumab Plus Olaparib Versus Pembrolizumab Plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous NSCLC. J Thorac Oncol. 2025 Feb;20(2):219-232. doi: 10.1016/j.jtho.2024.10.026. Epub 2024 Nov 7. PMID 39521434