Primary End Points Not Met With Pembrolizumab/Olaparib in NSCLC Trial

The phase 3 KEYLYNK-006 trial did not meet the primary end points of progression-free and overall survival in patients with metastatic nonsquamous non–small cell lung cancer.

The dual primary end points of the phase 3 KEYLYNK-006 trial (NCT03976323), which was exploring first-line pembrolizumab (Keytruda) plus olaparib (Lynparza) in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC), were not met, according to a press release from Merck.¹

The primary end points were overall survival (OS) and progression-free survival (PFS). The trial compared pembrolizumab plus olaparib vs pembrolizumab plus chemotherapy followed by pembrolizumab plus maintenance therapy. It was noted that the safety profile was consistent with previously reported results. Merck is working on sharing additional results with the community.

“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,” Gregory Lubiniecki, MD, vice president of Global Clinical Development at Merck Research Laboratories said in the press release. “These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous non–small cell lung cancer. We sincerely thank the patients and investigators for their important contributions to this study.”

A total of 1005 patients were enrolled in the induction portion and 672 had a complete or partial response with stable disease. Secondary end points of this trial included safety and health-related quality of life.

During induction, patients received intravenous (IV) pembrolizumab at 200 mg plus pemetrexed and either area under the curve IV carboplatin at 5 mg/mL/min or IV cisplatin at 75 mg/m² every 3 weeks for 4 cycles. During maintenance, those who achieved a complete or partial response or had stable disease after completing 4 cycles of therapy were randomly assigned to receive either IV pembrolizumab at 200 mg every 3 weeks for up to 31 cycles plus maintenance olaparib orally twice a day at 300 mg or 200 mg of IV pembrolizumab every 3 weeks for 31 cycles plus maintenance pemetrexed at 500 mg/m² every 3 weeks.

Patients were eligible for treatment if they had histologically or cytologically confirmed nonsquamous NSCLC; have confirmation that EGFR, ALK, or ROS1-directed therapy is not indicated; and have measurable disease.² Additionally, patients must have provided archival tumor tissue that was not previously irradiated, have had a life expectancy of at least 3 months, and an ECOG performance status of 0 or 1.

If patients have histology that is predominantly squamous, have an additional malignancy with progression in the past 3 years, and have active central nervous system metastases, they were not eligible for enrollment. Other exclusion criteria included having severe hypersensitivity to pembrolizumab, cisplatin, or carboplatin, having an active autoimmune disease, or having been diagnosed with an immunodeficiency.

In December 2023, Merck discontinued the phase 3 KEYLYNK-008 trial assessing pembrolizumab plus olaparib for patients with newly diagnosed metastatic squamous NSCLC.³ The trial did not meet the dual primary end points of OS and PFS. During the second interim analysis, there was no significant extension of time before tumor progression or death.

References

1. 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. News release. Merck. March 21, 2024. https://shorturl.at/yBCKT
2. 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). NCT03976323. Updated August 9, 2023. Accessed March 21, 2024. https://shorturl.at/arwIQ
3. For Merck, Lynparza fails to improve on Keytruda in first-line lung cancer. News release. Fierce Pharma. December 7, 2023. Accessed March 21, 2024. https://shorturl.at/bemAU