2024 World Conference on Lung Cancer (WCLC) - Posters-P3.12D.08 DCC-3116 In Combination with Sotorasib in Advanced or Metastatic KRASG12C-Mutant Cancers: First-in-human Phase 1/2 Study

P3.12D.08 DCC-3116 In Combination with Sotorasib in Advanced or Metastatic KRASG12C-Mutant Cancers: First-in-human Phase 1/2 Study

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The study presented at the 2024 World Conference on Lung Cancer investigates the phase 1/2 trial of DCC-3116 combined with sotorasib for treating advanced or metastatic KRASG12C-mutant cancers. KRASG12C mutations activate autophagy, which contributes to cancer cell survival. DCC-3116, a ULK1/2 inhibitor, targets this process, while sotorasib targets the KRASG12C mutation. The study aims to assess the safety, tolerability, and efficacy of this combination therapy.<br /><br />The trial consists of two parts: dose escalation and dose expansion. In the dose escalation phase, patients receive increasing doses of DCC-3116 with sotorasib to establish the recommended phase 2 dose (RP2D) while evaluating safety and tolerability. The dose expansion phase administers the RP2D to further assess antitumor activity, measured via RECIST v1.1 criteria, for objective response rate, disease control, and survival metrics.<br /><br />Key inclusion criteria include adults with advanced/metastatic cancer having the KRASG12C mutation and progression post-standard therapy. Exclusion criteria include recent anticancer treatment, incompatibility with study drugs, or previous treatment with KRASG12C inhibitors. Participants in dose escalation require only one prior line of anticancer therapy, whereas dose expansion participants must have non-small cell lung cancer (NSCLC) and no previous KRASG12C inhibitor exposure.<br /><br />Deciphera Pharmaceuticals sponsors the study (NCT04892017), currently enrolling participants. The objective is to explore the potential of inhibiting autophagy, implicated in cancer cell survival pathways, enhancing the effectiveness of targeted cancer treatments. Results may establish a new therapeutic strategy for KRASG12C-mutant cancers.<br /><br />This first-in-human study seeks to address the unmet needs in treating KRASG12C-mutant cancers by combining pathway inhibition with autophagy blockade, possibly leading to improved outcomes for patients with limited treatment options.

Asset Subtitle

Frederic Reu

Meta Tag

Speaker Frederic Reu

Topic Metastatic NSCLC – Targeted Therapy

Keywords

KRASG12C-mutant cancers

autophagy inhibition

DCC-3116

sotorasib

ULK1/2 inhibitor

dose escalation

dose expansion

RECIST v1.1

Deciphera Pharmaceuticals

NCT04892017