Merck Faces Setback as Keytruda Combination Therapy Falters in Two Lung Cancer Trials

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Merck Faces Setback as Keytruda Combination Therapy Falters in Two Lung Cancer Trials

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Merck Faces Setback as Keytruda Combination Therapy Falters in Two Lung Cancer Trials

Merck’s Keytruda Combination Therapy Faces Setback with Two Consecutive Lung Cancer Clinical Trial Failures!

On December 7, 2023, Merck announced the disappointing results of two trials involving the Keytruda (pembrolizumab) combination therapy.

The first trial, KEYLYNK-008, a Phase III trial, evaluated the efficacy of Keytruda in combination with the maintenance therapy drug Lynparza (olaparib), a PARP inhibitor, for the treatment of metastatic squamous non-small cell lung cancer (NSCLC) patients.

The second trial, KeyVibe-002, presented detailed data for the first time, focusing on the combination of Keytruda and TIGIT inhibitor vibostolimab in treating patients with metastatic non-small cell lung cancer (NSCLC) in a Phase II clinical trial.

1. Merck to Terminate Phase III Trial (KEYLYNK-008)

KEYLYNK-008 was a randomized, triple-blind, Phase III trial that enrolled approximately 857 patients to assess the effectiveness of Keytruda in combination with Lynparza for the treatment of non-small cell lung cancer. Following the interim analysis (IA3) data review, the Independent Data Monitoring Committee (DMC) recommended terminating the Phase III trial. According to Merck, the mid-term analysis did not demonstrate an improvement in overall survival (OS) when comparing Keytruda in combination with Lynparza to placebo treatment in patients with non-small cell lung cancer after chemotherapy, which was one of the study’s dual primary endpoints.

Additionally, the study’s other major endpoint, progression-free survival (PFS), did not reach statistical significance in the second interim analysis but showed numerical improvement compared to the control group. The safety profile of the trial was consistent with the safety observed in previous studies of individual therapies, with no new safety signals detected. Merck plans to release the complete details of this study at a later date.

2. KeyVibe-002 Results Unveiled at ESMO I-O 2023 Congress

KeyVibe-002, a randomized, partially blinded Phase II trial, investigated the efficacy of the Keytruda + TIGIT inhibitor vibostolimab combination or monotherapy compared to placebo plus monotherapy with docetaxel in the treatment of progressive metastatic NSCLC patients after immunotherapy and platinum doublet chemotherapy.

The study included 255 patients randomly assigned to three independent study groups (1:1:1). KeyVibe-002 had two primary objectives: to assess the efficacy of the combination therapy alone compared to standard docetaxel treatment and to evaluate the efficacy of adding the combination therapy to docetaxel compared to docetaxel alone in a blinded assessment.

Results showed that the combination of vibostolimab/pembrolizumab with docetaxel extended the median progression-free survival (PFS) by 2.4 months compared to docetaxel alone, but the result did not reach statistical significance (5.6 months vs. 3.2 months; HR=0.77 [95% CI, 0.53-1.13]; p=0.0910). Moreover, the monotherapy with vibostolimab/pembrolizumab did not improve median PFS compared to docetaxel alone (2.7 months vs. 3.2 months; HR=1.40 [95% CI, 0.96-2.02]; p=0.9622).

Key secondary endpoints of the study, including overall survival (OS), overall response rate (ORR), and duration of response (DOR), did not reach statistical significance. Specifically, compared to docetaxel alone, the combination of vibostolimab/pembrolizumab improved OS (HR=0.76 [95% CI, 0.50-1.15]); monotherapy with vibostolimab/pembrolizumab did not show improvement in OS (HR=1.05 [95% CI, 0.70-1.58]). The median OS for the vibostolimab/pembrolizumab combination with docetaxel was 10.2 months (95% CI, 8.6-14.9), monotherapy with vibostolimab/pembrolizumab was 7.5 months (95% CI, 5.2-13.4), and docetaxel alone was 8.8 months (95% CI, 6.4-11.1).

Patients receiving the combination therapy had an ORR of 29.9% (95% CI, 20.5-40.6), while those on monotherapy had ORRs of 6.0% (95% CI, 2.0-13.5) and 15.3% (95% CI, 8.4-24.7). The median DOR for the combination therapy group was 6.5 months (range 2.1+ to 15.4+ months), whereas the monotherapy groups with vibostolimab/pembrolizumab (range 2.6+ to 6.2+ months) and docetaxel alone (range 1.6-11.1+ months) did not reach statistical significance.

Additionally, Merck noted four treatment-related deaths in the vibostolimab, Keytruda, and docetaxel group, and one each in the vibostolimab, Keytruda, and docetaxel-alone groups.

Vibostolimab is Merck’s investigational anti-TIGIT antibody designed to restore anti-tumor activity by blocking the TIGIT receptor’s interaction with its ligands (CD112 and CD155), thereby activating T lymphocytes that aid in destroying tumor cells.

Despite the failure of the KeyVibe-002 trial, Merck remains confident in the PD-1+TIGIT inhibitor combination therapy. Eliav Barr, Chief Medical Officer of Merck, stated that Merck has initiated at least four critical lung cancer trials targeting the Keytruda + vibostolimab combination, including KeyVibe-003, KeyVibe-006, KeyVibe-007, and KeyVibe-008.

Merck Faces Setback as Keytruda Combination Therapy Falters in Two Lung Cancer Trials

Reference:
[1] Merck’s Keytruda, Anti-TIGIT Combo Fails Phase II NSCLC Trial. BioSpace. Published: Dec 07, 2023, By Tyler Patchen.

(source:internet, reference only)

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