Phase 3 Trial of Pembrolizumab with Olaparib Did Not Meet Endpoints Among Individuals with NSCLC


Pembrolizumab in combination with chemotherapy followed by maintenance olaparib did not meet its pre-specified statistical criteria of overall survival or progression free survival.

Merck has announced that its phase 3 KEYLYNK-006 trial (NCT03976323) that assessed pembrolizumab (Keytruda), an anti-PD-1 therapy, in combination with olaparib (Lynparza), a PARP inhibitor, did not meet the primary endpoint of overall survival (OS) and progression-free survival (PFS). The study was used as a first line of treatment among evident individuals with metastatic nonsquamous non-small cell lung cancer (NSCLC).

Human Lung model illness, Lung cancer and lung disease. Generative AI - Image credit: Royalty-Free |

Image credit: Royalty-Free |

The study authors noted that 2022 had 2.4 million new cases and 1.8 million deaths from lung cancer worldwide. Among the 2.4 million cases, NSCLC accounted for 80%. However, the 2024 overall 5-year survival rate among individual diagnosed with lung cancer is 25% in the US. This emphasizes the need for improved survival rates and early detection of disease.

About the Clinical Trial

Trial Name: 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) ID: NCT03976323

Sponsor: Merck Sharp & Dohme LLC

Study Completion (Estimated): January 2025

“As lung cancer continues to be the leading cause of cancer death worldwide, we are committed to exploring [pembrolizumab]-based combinations and novel candidates that may further help improve patient outcomes,” said Gregory Lubiniecki, MD, vice president and global clinical development at Merck Research Laboratories, in a press release.

Pembrolizumab is an anti-programmed death receptor-1 (PD-1) that is aimed to increase the body’s immune system to detect and attack tumor cells. However, when combined with pemetrexed and platinum chemotherapy, it can treat individuals with metastatic squamous NSCLC.

The randomized, open-label, phase 3 trial evaluated pembrolizumab with chemotherapy (pemetrexed plus carboplatin or cisplatin), continued by pembrolizumab with olaparib or pembrolizumab with pemetrexed. The individuals eligible for first-line treatment could not have epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or proto-oncogene tyrosine-protein kinase (ROS1) genomic tumor aberrations. About 1005 individuals were included in the induction phase and 672 individuals were randomly assigned with a complete or partial response, or with stable disease, according to study authors. Individuals in the induction group received 200 mg of pembrolizumab with pemetrexed and a choice of platinum chemotherapy every 3 weeks for 4 cycles. Individuals with complete or partial response with stable disease after the 4 cycles were assigned random treatment with pembrolizumab and 300 mg of olaparib twice daily, or pembrolizumab with pemetrexed.

However, pembrolizumab in combination with chemotherapy followed by maintenance olaparib, did not meet its pre-specified statistical criteria of OS or PFS. The results were compared to pembrolizumab with pemetrexed plus carboplatin or cisplatin, followed by maintenance pemetrexed, which displayed better outcomes. However, the safety profiles were consistent of prior reported individual therapies.

Despite not meeting the primary endpoints, the study authors noted that a full evaluation of the study is ongoing.

“These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous [NSCLC]. We sincerely thank the patients and investigators for their important contributions to this study,” said Lubiniecki in a press release.

Merck Provides Update on Phase 3 KEYLYNK-006 Trial Evaluating KEYTRUDA® (pembrolizumab) Plus Maintenance Lynparza (olaparib) for Certain Patients With Metastatic Nonsquamous Non-Small Cell Lung Cancer. Merck. News release. March 21, 2024. Accessed March 21, 2024.
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