Prof. ByoungChul Cho, MD, Ph.D. from the Yonsie University College of Medicine discusses NACLC for Quavonlimab (MK-1308), a Novel Investigational Anti-CTLA-4 Antibody, in Combination With KEYTRUDA Were Presented; Phase 3 Study for the Combination Planned in First-Line Advanced NSCLC.
KENILWORTH, N.J."(BUSINESS WIRE)"Merck (NYSE: MRK), known as MSD outside the U.S. and Canada, today declared positive results from two of the company’s leading lung cancer clinical development studies evaluating KEYTRUDA, Merck’s anti-PD-1 treatment: KEYTRUDA in combination with chemotherapy (KEYNOTE-021 [Cohort G]) and KEYTRUDA in combination with quavonlimab (MK-1308), Merck’s anti-PD-1 treatment, KEYTRUDA in combination with chemotherapy (KEYNOTE-021 [Cohort G])
First-line treatment with KEYTRUDA in conjunction with chemotherapy (n=60) in KEYNOTE-021 (Cohort G) showed a substantial increase in objective response rates (58% vs. 33%), progression-free survival (HR=0.54 [95 % CI, 0.35-0.83]) and a sustained long-term survival advantage (HR=0.71 [95 % CI, 0.45-1.12]) versus chemotherapy alone (n=63) in adva patients. There were no EGFR or ALK genomic tumor aberrations in the patients in Cohort G. In conjunction with chemotherapy for the first-line treatment of NSCLC, these results represent the longest follow-up evidence for an anti-PD-1 / PD-L1 treatment. In addition, revised follow-up results from the quavonlimab phase 1/2 trial in combination with KEYTRUDA showed promising anti-tumor activity and an appropriate safety profile for first-line therapy in patients with advanced NSCLC (# TS01.02 poster).
At the IASLC 2020 North America Conference on Lung Cancer held by the International Association for the Study of Lung Cancer on Friday, Oct. 16, findings from both studies were discussed. Via @Merck, follow Merck on Twitter and stay up to date with NACLC news and updates by using the # NACLC20 hashtag.
(Featured Poster # OFP01.02) KEYTRUDA in Conjunction With Chemotherapy: Long-Term Results in Advanced NSCLC From KEYNOTE-021 (Cohort G)
New data from KEYNOTE-021 Cohort G (NCT02039674) showed a substantial increase in objective response (ORR) rates, progression-free survival (PFS), and sustained long-term survival advantage for KEYTRUDA in combination with pemetrexed (ALIMTA ®) and platinum chemotherapy versus pemetrexed and platinum chemotherapy alone after a median follow-up span of four years (49.4 months; range, 43. The Phase 1/2 multi-cohort, multi-center, open-label cohort G trial assessed KEYTRUDA as first-line treatment in patients with advanced non-squamous NSCLC in conjunction with chemotherapy (n=60) versus chemotherapy alone (n=63). There were no EGFR or ALK genomic tumor aberrations in the patients in Cohort G.
KEYNOTE-021 (Cohort G) results found that 50 % of patients treated with KEYTRUDA in conjunction with chemotherapy were 3 years of age, compared with 37% of patients treated with chemotherapy alone. KEYTRUDA also decreased the risk of death by 29 percent in conjunction with chemotherapy (HR=0.71 [95 percent CI, 0.45-1.12]) versus chemotherapy alone, with a median overall survival ( OS) of 34.5 versus 21.1 months. Despite a 70 percent (n=43/61) successful crossover rate from chemotherapy to anti-PD-1 / PD-L1 treatment, the OS advantage was observed, including 28 patients who were treated as part of the on-study crossover with KEYTRUDA.
In conjunction with chemotherapy, the ORR was 58 percent for KEYTRUDA versus 33 percent for chemotherapy alone. KEYTRUDA also decreased the risk of disease development or death by 46 percent over chemotherapy (HR=0.54 [95 percent CI, 0.35-0.83]), with a median PFS of 24.5 months (range, 9.7 to 36.3) versus 9.9 months (range, 6.2 to 15.2). For patients who received KEYTRUDA in conjunction with chemotherapy, the median three-year PFS rate was 37 percent versus 16 percent for those who received chemotherapy alone. In conjunction with chemotherapy, the median period of response (DOR) was more than one year longer with KEYTRUDA (36.3 months; range, 1.4 + to 49.3 +) versus chemotherapy alone (22.8 months; range, 2.8 + to 47.2 +). In addition, 51% of patients treated with KEYTRUDA in conjunction with chemotherapy had responses that lasted for three years, compared with 47% who received chemotherapy alone.
Notably, 92% of patients who completed two years of KEYTRUDA therapy were 3-year-old (n=11/12). Objective response was experienced in all 12 patients and the estimated three-year DOR rate was 100 percent (median DOR not reached [NR]; 11.7 + to 49.3 + months range).
No new safety signals were established for KEYTRUDA in combination with chemotherapy during long-term follow-up. 39 percent of those receiving KEYTRUDA in conjunction with chemotherapy and 31 percent of those receiving chemotherapy alone experienced Grade 3-5 treatment-related adverse effects (TRAEs) for all those treated. In 17 percent of the patients who received KEYTRUDA in conjunction with chemotherapy and 16 percent of those who received chemotherapy alone, grade 3-5 TRAEs that contributed to discontinuation occurred. In 2 percent (n=1) of patients who received KEYTRUDA in combination with chemotherapy and 3 percent (n=2) of those who received chemotherapy alone, grade 3-5 TRAEs that contributed to death occurred.
In partnership with Eli Lilly and Company, the makers of pemetrexed (ALIMTA ®), the KEYNOTE-021 (Cohort G) trial was performed.
In combination with KEYTRUDA, Quavonlimab (anti-CLTA-4): Step 1/2 Results in advanced NSCLC (Poster # TS01.02)
Quavonlimab, Merck’s experimental anti-CTLA-4 therapy, was tested in this first-in-human, open-label, multi-arm Phase 1/2 (NCT03179436) trial in conjunction with KEYTRUDA as a first-line treatment in patients with advanced NSCLC. During the dose-confirmation process, patients were given quavonlimab (25 mg or 75 mg) in combination with KEYTRUDA every three weeks (Q3W) or every six weeks (Q6W) (200 mg Q3W for up to 35 cycles). The primary objective of the analysis was protection and tolerability; ORR per RECIST v1.1 by blinded independent central review (BICR), PFS, OS, and DOR were included in the secondary and exploratory objectives. The response based on PD-L1 status was retrospectively evaluated as a continuous variable using the tumor proportion score (TPS).
The results showed that quavonlimab had an appropriate safety profile with no unforeseen toxicities in combination with KEYTRUDA, and suggested promoting anti-tumor activity. There were all-grade adverse events in 98 percent of patients; 85 percent of patients had TRAEs. Grade ⇠3 TRAEs occurred in 36 percent of patients across all treatment arms and increased alanine aminotransferase (8 percent), pneumonitis (8 percent), and increased aspartate aminotransferase (6 percent) were the most common TRAEs (> 10 percent in either arm).
Study findings demonstrated the effect of quavonlimab in conjunction with KEYTRUDA across secondary and exploratory endpoints, like ORR, PFS, OS, and DOR, at 16.9 months of median follow-up (range, 7.0 to 21.3). Regardless of PD-L1 expression, responses to quavonlimab in combination with KEYTRUDA were observed with higher TPS scores significantly correlated with better response (one-sided p=0.015). These safety and efficacy data support the 25 mg Q6W dose when used in conjunction with KEYTRUDA, as the approved Phase 2 dose of quavonlimab.