Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Non-squamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: Carcinoma, Non-squamous Non-small-cell Lung

Treatments: Drug: Carboplatin; Drug: Cisplatin; Drug: Olaparib; Biological: Pembrolizumab; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT03976323

194895 (Registry Identifier)

7339-006

KEYLYNK-006 (Other Identifier)

2023-509774-40 (Other Identifier)

U1111-1300-7107 (Other Identifier)

2018-004720-11 (EudraCT Number)

MK-7339-006 (Other Identifier)

Details and patient eligibility

About

The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs pembrolizumab plus maintenance pemetrexed for the treatment of nonsquamous 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 (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).

Full description

This study has 2 phases: an Induction Phase (4 Cycles) and a Maintenance Phase (Up to 31 cycles of pembrolizumab). In the Induction Phase, participants receive pembrolizumab plus pemetrexed plus platinum (carboplatin or cisplatin). In the Maintenance Phase, participants with a partial or complete disease response or with stable disease after completing four cycles of induction therapy and who meet eligibility criteria will be randomly assigned to receive pembrolizumab plus maintenance olaparib OR pembrolizumab plus maintenance pemetrexed. In the Maintenance Phase, participants receive pembrolizumab for up to 31 cycles plus maintenance olaparib OR maintenance pemetrexed until progressive disease (PD), intolerable toxicities, or physician decision.

Enrollment: 672 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
14. Has completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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672 participants in 2 patient groups

Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib

Experimental group

Description:

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m\^2 IV on Day 1 of each 21-day 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 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21-day cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until progressive disease, physician decision or intolerable toxicity.

Treatment:

Drug: Pemetrexed

Biological: Pembrolizumab

Drug: Olaparib

Drug: Cisplatin

Drug: Carboplatin

Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed

Active Comparator group

Description:

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m\^2 IV on Day 1 of each 21-day 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 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21 day-cycle for up to 31 cycles PLUS maintenance pemetrexed IV 500 mg/m\^2 on Day 1 of each 21-day cycle. In the Maintenance Phase, the participant continues to receive maintenance pemetrexed until progressive disease, physician decision or intolerable toxicity.

Treatment:

Drug: Pemetrexed

Biological: Pembrolizumab

Drug: Cisplatin

Drug: Carboplatin