Pneumologie 2025; 79(S 01): S54
DOI: 10.1055/s-0045-1804654
Abstracts
B1 – Pneumologische Onkologie

Efficacy and Safety of Olomorasib with Pembrolizumab+Chemotherapy as First Line Treatment in Patients with KRAS G12C-Mutant Advanced NSCLC

Authors

  • Y Fujiwara

    1   Aichi Cancer Center Hospital

  • N Ammakkanavar

    2   Community Health Network

  • A Hollebecque

    3   Gustave Roussy; Gustave Roussy; Department of Adult Medicine

  • Y Goroff

    4   Department of Medicine, Memorial Sloan Kettering Cancer Center

  • D Lee

    5   Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center

  • T Burns

    6   Department of Medicine, Division of Hematology Oncology; University of Pittsburgh Medical Center Hillman Cancer Center

  • P Cassier

    7   Department of Medical Oncology, Centre Léon Bérard

  • J Youn Han

    8   National Cancer Center Korea; National Cancer Center

  • A Italiano

    9   Early Phase Trials Unit, Institut Bergonié

  • T Koyama

    10   Department of Experimental Therapeutics, National Cancer Center Hospital

  • B Yong Shim

    11   Department of Medical Oncology, The Catholic University of Korea, St. Vincent's Hospital

  • R Heist

    12   Massachusetts General Hospital

  • J Sabari

    13   Nyu Langone Health – Perlmutter & Long Island

  • A Spira

    14   Virginia Cancer Specialists; Virginia Cancer Specialists

  • J Bodor

    15   Fox Chase Cancer Center

  • Q Chu

    16   Alberta Health Services Cross Cancer Institute

  • G Durm

    17   Indiana University (Iu) Melvin and Bren Simon Cancer Center

  • N Singhal

    18   Cancer Research Centre

  • M Chisamore

    19   Merck & Co., Inc.

  • A Fink

    20   Loxo@lilly

  • M Willard

    20   Loxo@lilly

  • G Oxnard

    20   Loxo@lilly

  • K Dragnev

    21   Dartmouth Cancer Center

  • M Thomas

    22   University Hospital Heidelberg; Thoraxklinik at Heidelberg; Department of Thoracic Oncology
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Olomorasib, a potent, second-generation KRAS G12C inhibitor has demonstrated promising activity in KRAS G12C-mutant non-small cell lung cancer (NSCLC) as monotherapy and in combination with pembrolizumab. Here, we report the first clinical data describing olomorasib in combination with chemo-immunotherapy (chemo – IO).

The phase 1 trial (NCT04956640) enrolled patients (pts) with advanced KRAS G12C-mutant NSCLC into multiple cohorts. Two doses of olomorasib (50 mg and 100 mg, orally BID) in combination with standard chemotherapy (CT) platinum/pemetrexed and pembrolizumab were studied.

Of the 89 pts who received olomorasib+pembrolizumab, a subset of 20 pts received CT. Median age was 68 years; PD-L1 was negative in 11 pts, low in 7, high in 1 and unknown in 1. Prior to enrollment 8 pts received 1 cycle of SOC therapy. Median duration of therapy was 4.2 months and 16 pts remained on study therapy at time of data-cut. All grade TRAEs in>20% of pts were anemia, nausea, decreased appetite, fatigue, and neutrophil count decreased; grade≥3 TRAEs in≥10% of pts were diarrhea and decrease in neutrophil count, WBC count, and platelet count. Grade 3 immune-related AEs included elevated ALT/AST and pneumonitis. TRAEs resulted in olomorasib dose reduction in 2 pts. Hematologic toxicity delayed subsequent cycle of chemo in 3 pts. Among the 18 efficacy-evaluable pts, ORR was 44% (95% CI, 22-69) and disease control rate was 83% (95% CI, 59-96).

Olomorasib in combination with chemo-IO demonstrated a favorable safety profile, consistent with the safety profiles observed with other combinations of CT and targeted therapy. The ORR was lower in this first-line cohort compared to the prior report with olomorasib+pembrolizumab, representative of the higher risk, PD-L1 negative pts enrolled to chemo-IO backbone. A global, registrational study investigating this combination in first-line NSCLC is currently enrolling (SUNRAY-01, NCT06119581).


Publication History

Article published online:
18 March 2025

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