The phase I trial of sotorasib, a KRASG12C inhibitor, demonstrated a favorable safety profile and preliminary antitumor activity in pts with advanced solid tumors harboring KRAS p.G12C. Here, we present durability of clinical benefit and biomarker data in pts with NSCLC.
Key eligibility criteria include KRAS p.G12C mutation and prior systemic anticancer treatment (tx). Primary endpoint is safety; key secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS). KRAS p.G12C mutant allele frequency (MAF) and PD-L1 level were examined.
As of July 17, 2019, 40 pts with NSCLC (22 female [55.0%], median age: 68.0 years [range: 49-77]) were enrolled. Data cutoff date was March 25, 2020. 31 (77.5%) and 19 pts (47.5%) received ≥ 2 and 3 prior lines of therapy, respectively. Median follow-up was 10.2 (range: 8.3–19.0) months (mos). 3 pts (7.5%) had adverse events leading to discontinuation. There were no dose-limiting toxicities or fatal tx-related adverse events. Median PFS for all pts was 6.9 (range: 1.2–13.9) mos. ORR was 30% (95% Cl, 16.56–46.53). DOR ranged from 1.6 (+) to 12.7 mos, with 7 of 12 responders still in response at data cutoff. DCR was 92.5% (95% Cl, 79.61–98.43). 18 pts (45.0%) had progressive disease. At data cutoff, 10 pts (25.0%) were on study without disease progression, and 9 pts (22.5%) died. 18 pts (45.0%) (5 partial response (PR), 12 stable disease (SD), 1 progressive disease (PD)) had KRAS p.G12C MAF data available. There was no significant association between KRAS p.G12C MAF and response (Wilcoxon P = 0.80 for PR vs SD). 11 pts (27.5%) had PD-L1 data available. The median PD-L1 tumor proportion score [TPS] was 3% (range: 1–5) in 2 pts with PR, 0% (range: 0–0) in 8 pts with SD, and 75% (range: 75–75) in the pt with PD (Wilcoxon P = 0.044 for PR vs. SD).
In pts with heavily pretreated NSCLC, durable responses to sotorasib were seen, with the majority of pts achieving disease control leading to a median PFS of 6.9 months. The current limited dataset suggests that neither KRAS p.G12C MAF nor PD-L1 expression level predicts response to sotorasib.
NCT03600883.
Medical writing support was provided by Liz Leight (Amgen Inc.).
Amgen Inc.
Amgen Inc.
D.S. Hong: Research grant/Funding (institution), Non-remunerated activity/ies: Bayer; Honoraria (self), Research grant/Funding (institution): Loxo; Mirati; Research grant/Funding (institution): Lilly; Genentech; Pfizer; Amgen; Ignyta; Merck; Daichii-Sanko; Eisai; Adaptimmune; AbbVie; AstraZeneca; BMS; Genmab; Infinity; Kite; MedImmune; Molecular Template, Novartis, Takeda; Non-remunerated activity/ies: Baxter, Guidepoint global, Oncoresponse, Janssen, Molecular Match, outside the submitted work. Y-J. Bang: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Novartis; Genentech/Roche; MSD; Merck Serano; Bayer; BMS; Eli Lilly; Taiho; Daiich-Sankyo; Astellas; BeiGene; GreenCross; Advisory/Consultancy: Samyang Biopharm; Hanmi; Advisory/Consultancy, Research grant/Funding (institution): Genexine; Research grant/Funding (institution): GSK; Pfizer; Boeringer Ingelheim; MacroGenics, Boston Biomedical, FivePrime, Curis, Takeda, Ono, CKD Pharma. F. Barlesi: Honoraria (self), Leadership role, Research grant/Funding (institution), Principal Investigator for sponsored clinical trial: AstraZeneca; Bristol-Myers Squibb; F. Hoffmann-La Roche Ltd; Honoraria (self), Research grant/Funding (institution), Principal Investigator for sponsored clinical trial: Merck; Honoraria (self), Research grant/Funding (institution): Bayer; Boehringer Ingelheim; Eli Lilly Oncology; Novartis; MSD; Pierre Fabre; Pfizer; Takeda; Research grant/Funding (institution): AbbVie; ACEA; Amgen; Eisai; Genentech; Ipsen; Ignyta; Innate Pharma, Loxo, MedImmune, Sanofi-Aventis. G. Durm: Research grant/Funding (institution): Merck; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bristol-Myers Squibb; Non-remunerated activity/ies: Amgen. G.S. Falchook: Honoraria (self): Wolters Kluwer; Advisory/Consultancy, Travel/Accommodation/Expenses: Fujifilm; EMD Serono; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Millennium; Sarah Cannon Research Institute; Honoraria (self): Total Health Conferencing; Rocky Mountain Oncology Society; Research grant/Funding (institution): 3-V Biosciences; Abbisko; Abbvie; ADC Therapeutics; Aileron; American Society of Clinical Oncology; Amgen; ARMO; AstraZeneca; BeiGene; Bioatla; Celldex, Celgene, Ciclomed, Curegenix, Curis, Cyteir, Daiichi, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Exelixis, Fujifilm, Genmab, GlaxoSmithKline, Hutchison MediPharma, Ignyta, Incyte, Jacobio, Jounce, Kolltan, Loxo, MedImmune, Millennium, Merc. K. Park: Advisory/Consultancy: Amgen. J.H. Strickler: Advisory/Consultancy, Research grant/Funding (institution): Amgen. T.F. Burns: Advisory/Consultancy: Novartis; Advisory/Consultancy: Blueprint Medicine; Advisory/Consultancy: Thermo Fisher Scientific. J. Kim; A. Ang; J.R. Lipford; G. Ngarmchamnanrith; A. Anderson: Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen. B.T. Li: Advisory/Consultancy: Thermo Fisher Scientific; Guardant Health; Mersana Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Hengrui Therapeutics; Eli Lilly; Travel/Accommodation/Expenses: Resolution Bioscience; Research grant/Funding (institution), Travel/Accommodation/Expenses: MORE Health; Research grant/Funding (institution): Amgen; Daiichi Sankyo; AstraZeneca; BioMedValley Discoveries; Illumina; Research grant/Funding (institution): GRAIL ; Research grant/Funding (institution): Guardant Health. All other authors have declared no conflicts of interest.