Found 1 Presentation For Request "434P"

Colorectal cancer

434P - CodeBreaK 101 subprotocol H: Phase Ib study evaluating combination of sotorasib (Soto), a KRASG12C inhibitor, and panitumumab (PMab), an EGFR inhibitor, in advanced KRAS p.G12C-mutated colorectal cancer (CRC)

Presentation Number
434P
Speakers
  • Marwan Fakih (Duarte, CA, United States of America)

Abstract

Background

Soto, a specific, irreversible KRASG12C inhibitor, has monotherapy clinical activity in KRAS p.G12C-mutated solid tumors, with an objective response rate of 7.1% for heavily pretreated CRC in the CodeBreaK 100 phase I trial. KRASG12C blockade can lead to accumulation of activated EGFR. Combining Soto with an EGFR inhibitor may produce synergistic antitumor activity. The safety and efficacy of Soto with PMab, a monoclonal antibody specific to EGFR, in KRAS p.G12C-mutated CRC are being evaluated in this ongoing phase Ib study (NCT04185883).

Methods

This study includes a dose exploration phase to identify a safe/tolerable daily oral dose of Soto with PMab (6mg/kg IV Q2W) in patients (pts) with previously treated mCRC, and a dose expansion phase. Dose exploration is reported.

Results

As of 4/23/21, 8 pts (5 female, median age: 60.5 yrs [range: 31-79]) were enrolled in dose exploration with 960 mg QD Soto and 6mg/kg IV Q2W PMab. Median number of lines of therapy for metastatic disease was 3.5 (range 1-10); 5 pts had prior Soto. Median treatment (tx) duration was 4.4 months (range: 1.4, 8.8). No dose limiting toxicities (DLTs) were observed during the DLT evaluation period (first 28 days). Tx-related adverse events (TRAEs) of any grade related to Soto or PMab were reported for 4 and 8 pts, respectively. No grade 4 or fatal TRAEs occurred. Two pts had PMab TRAEs leading to dose modification of PMab (1–dermatitis acneiform, 1–dry skin, rash, hypokalemia, hypomagnesemia) and 1 pt had a Soto TRAE leading to dose modification of Soto (diarrhea). There was 1 confirmed partial response, 5 stable disease (SD), 1 progressive disease (PD), and 1 not evaluated but with clinical PD. Of pts with prior Soto, 4 had decrease in sum of target lesions; 4 had SD and 1 with PD developed new lesions despite a decrease in size of target lesions. Sotorasib exposures were similar to those observed in monotherapy study.

Conclusions

Combination of Soto (960 mg QD) and PMab (6mg/kg IV Q2W) was safe and tolerable with promising efficacy in heavily pretreated pts with KRAS p.G12C-mutated CRC. AEs are consistent with known AEs for Soto and PMab. Updated safety and efficacy data will be presented.

Clinical trial identification

NCT04185883.

Editorial acknowledgement

Medical writing support was provided by Yang Li and Liz Leight (Amgen Inc.).

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

M. Fakih: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Array BioPharma; Bayer; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis. G.S. Falchook: Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Advisory Role: Fujifilm; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Funding, Travel: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel: EMD Serono; Fujifilm; Millennium;: Sarah Cannon Research Institute; Financial Interests, Personal, Invited Speaker: Total Health Conferencing; Rocky Mountain Oncology Society; Financial Interests, Institutional, Funding, research funding: 3-V Biosciences; Abbisko; AbbVie; ADC Therapeutics; Aileron; American Society of Clinical Oncology; Amgen; ARMO; AstraZeneca; BeiGene; Bioatla; Biothera; 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; Merck; miRNA Therapeutics; National Institutes of Health; Novartis; OncoMed; Oncorus; Oncothyreon; Poseida; Precision Oncology; Prelude; Regeneron; Rgenix; Ribon; Strategia; Syndax; Taiho; Takeda; Tarveda; Tesaro; Tocagen; Turning Point Therapeutics; U.T. MD Anderson Cancer Center; Vegenics; Xencor. D.S. Hong: Financial Interests, Institutional, Research Grant: Bayer; Lilly; Genentech; LOXO; Pfizer; Amgen; Mirati; Ignyta; Merck; Daiichi Sankyo; Eisai; Adaptimmune; AbbVie; Astra-Zeneca; BMS; Genmab; Infinity; Kite; Kyowa; Medimmune; Molecular Template; Novartis; Takeda; Financial Interests, Personal, Other: Mirna; LOXO; Bayer; Baxter; Guidepoint Global; Oncoresponse; Janssen; Molecular Match. R.D. Yaeger: Financial Interests, Personal, Advisory Role: Array BioPharma/Pfizer; Natera; Mirati Therapeutics; Financial Interests, Institutional, Funding, research funding: Pfizer; Boehringer Ingelheim. E. Chan: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. O. Mather: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. P. Cardona: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. T. Dai: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. J. Strickler: Financial Interests, Personal, Advisory Board: Amgen; AstraZeneca; Bayer; Natera; Pfizer; SeaGen; Viatris; Financial Interests, Personal, Other, Consulting: Mereo; Non-Financial Interests, Institutional, Other, Coordinating PI: Amgen; Exelixis; Non-Financial Interests, Institutional, Principal Investigator, local PI: AbbVie; AStar D3; AstraZeneca; Curegenix; Daiichi Sankyo; Leap Therapeutics; Nektar; Roche Genentech; Sanofi; SeaGen.

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