A Study of Pembrolizumab (MK-3475) With or Without Maintenance Olaparib in First-line Metastatic Squamous Non-small Cell Lung Cancer (NSCLC, MK-7339-008/KEYLYNK-008)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: Carcinoma, Squamous Cell, Non-small-cell Lung

Treatments: Drug: Olaparib; Drug: Paclitaxel; Drug: Carboplatin; Drug: Placebo; Biological: Pembrolizumab; Drug: Nab-paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT03976362

7339-008

194894 (Registry Identifier)

KEYLYNK-008 (Other Identifier)

MK-7339-008 (Other Identifier)

2018-004721-88 (EudraCT Number)

Details and patient eligibility

About

The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs. pembrolizumab plus maintenance olaparib placebo for the treatment of squamous NSCLC. The study's 2 primary hypotheses are:

1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to progression-free survival (PFS) per RECIST 1.1 by blinded independent clinical review (BICR).
2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to overall survival (OS).

As of Amendment 07, there will be no further analyses for OS and patient-reported outcome assessments.

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 carboplatin plus a taxane (paclitaxel or nab-paclitaxel). 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 olaparib placebo. In the Maintenance Phase, participants randomly assigned to receive pembrolizumab for up to 31 cycles plus maintenance olaparib OR maintenance olaparib placebo until centrally verified progressive disease (PD), intolerable toxicities, or physician decision.

As of Amendment 07, participants actively taking placebo will discontinue taking the placebo intervention and continue in the study.

Enrollment: 591 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Have a histologically or cytologically confirmed diagnosis squamous NSCLC.

2. Have Stage IV squamous NSCLC.

3. Have measurable disease based on RECIST 1.1.

4. Have not received prior systemic treatment for their advanced/metastatic NSCLC.

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 receive study intervention(s). 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 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

7. Have a life expectancy of at least 3 months.

8. Has adequate organ function.

9. 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.

10. Male participants must refrain from donating sperm during the treatment period and for 180 days afterwards.

Exclusion criteria

1. Has non-squamous 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 metastases and/or carcinomatous meningitis.
4. Has a known hypersensitivity to any components or excipients of carboplatin, paclitaxel or nab-paclitaxel, or olaparib.
5. Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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591 participants in 2 patient groups

Pembrolizumab + Carboplatin + Taxane + 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 PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). 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 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 centrally verified progressive disease, physician decision or intolerable toxicity.

Treatment:

Drug: Nab-paclitaxel

Biological: Pembrolizumab

Drug: Carboplatin

Drug: Olaparib

Drug: Paclitaxel

Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo

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 PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). 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 for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.

Treatment:

Drug: Nab-paclitaxel

Biological: Pembrolizumab

Drug: Carboplatin

Drug: Placebo

Drug: Paclitaxel