989P - Sotorasib in advanced KRAS p.G12C-mutated non-small cell lung cancer (NSCLC): Safety and efficacy data from the global expanded access program (EAP)

Background

The sotorasib EAP provided compassionate use of sotorasib, a first-in-class KRAS G12C inhibitor, prior to local regulatory approvals. Here we present data from 2 global protocols under the EAP (Amgen study 20190436 [study-436] and 20190442 [study-442]) evaluating the safety and efficacy of sotorasib in patients (pts) with advanced KRAS p.G12C–mutated NSCLC beyond the traditional registrational trial setting.

Methods

Pts, including those with ECOG PS 2, treated or untreated brain metastases, and additional co-morbidities, were enrolled in 6 countries (USA, ITA, BRA, ISR, ESP, TWN) across 52 centers. The study was primarily designed to assess the safety of sotorasib 960 mg QD. Real-world progression-free survival (rwPFS) was estimated for study-436 (allowed for long-term follow-up) based on time from start of treatment to end of protocol due to disease progression or death, any death before new anti-cancer therapy, or end of commercial sotorasib, whichever occurred earlier.

Results

Under 2 EAP protocols, 137 pts received sotorasib. At baseline, pts had received a median of 2 (up to 7) prior lines of anticancer therapy, 29 (21%) pts had ECOG PS 2, and 36 (26%) had brain metastases (75% treated, 25% untreated). Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 32 (23%) pts; elevated AST and ALT (both 7 [5%] pts) were the most frequent. No suspected Hy’s law cases occurred. TRAEs leading to discontinuation and dose interruption/reduction of sotorasib occurred in 9 (7%) and 34 (25%) pts, respectively. TRAEs were similar, regardless of ECOG status or brain metastases at baseline. In study-436, median rwPFS was 6.4 months and subgroups of clinical interest are summarized (Table). Table: 989P

CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; NE, not estimable; rwPFS, real-world progression-free survival^aIn study-436, 30/92 (33%) patients switched to commercial supply. Patients who discontinued commercial supply were deemed to have progressed.^bMedian follow-up was 7.4 months; data cut-off date: April 1, 2022.

Conclusions

In this first analysis of the sotorasib EAP, which included pts with poor ECOG status and untreated brain metastases, the safety and rwPFS of sotorasib were consistent with the profile observed in clinical trials. Table

Clinical trial identification

NCT04667234 (Amgen study 20190436); First submitted: December 8, 2020.

Editorial acknowledgement

Medical writing assistance was provided by Liz Leight, an employee of Amgen Inc., and Advait A. Joshi of Cactus Life Sciences (part of Cactus Communications), which was funded by Amgen, Inc.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

M. Awad: Financial Interests, Personal, Other, Consultancy role: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, ArcherDX, Mirati, NextCure, Novartis, EMD Serono; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Genentech, Bristol-Myers Squibb. G. Pelizzari: Financial Interests, Personal, Other, Consultancy role: MSD, AstraZeneca, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Other, Travel expenses: Eli Lilly. J.P. Stevenson: Financial Interests, Personal, Advisory Board, Consultancy role: BeiGene, Novartis, Medtronic, Trizell Inc; Financial Interests, Institutional, Research Grant: Merck, EMD Serono, Amgen. M. Majem Tarruella: Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Other, Personal fees: BMS, MSD, Boehringer Ingelheim, Astra Zenenca, Roche, Kyowa Kyrin, Pierre Fabre, Novartis, Sanofi; Non-Financial Interests, Personal, Other: MSD, Boehringer Ingelheim, AstraZeneca, Roche, Lilly. W.J. Petty: Financial Interests, Personal, Other, Consultancy role: Mirati. E. Arriola: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Roche. J. de Castro: Financial Interests, Personal, Other, Educational fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp and Dohme, Roche; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithkline, Janssen-Cilag, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda. I. Morbeck: Financial Interests, Institutional, Research Grant: AstraZeneca, Janssen; Financial Interests, Personal, Other, Consulting fees: BMS, MSD, AstraZeneca, Bayer; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, MSD, Janssen, Bayer, Astellas, Ipsen; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, MSD; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: MSD, AstraZeneca, BMS. J.R. Bauman: Financial Interests, Personal, Advisory Board: Kura, Janssen, Pfizer, Blueprint Medicine, Lilly, Merck, Mirati, Turning Point Therapeutics, BeiGene. L. Toschi: Financial Interests, Personal, Other, Honoraria: Sanofi, MSD, Eli Lilly, Roche, AstraZeneca, Pfizer, BMS. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost; Financial Interests, Personal, Stocks/Shares: Nixio; Financial Interests, Institutional, Research Grant: BMS. A. Azkárate Martínez: Financial Interests, Personal, Advisory Board: Amgen. C. Xia: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. A. Meloni: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. C. Obiozor: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Eli Lilly, Novartis, BeiGene, Amgen; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen; Financial Interests, Institutional, Invited Speaker, IIT: MSD, BI; Non-Financial Interests, Leadership Role, President of this European advocacy: WALCE. All other authors have declared no conflicts of interest.