Dr Negrao on JDQ443 Plus TNO155 in Advanced, KRAS G12C–Mutated Solid Tumors

Marcelo Vailati Negrao, MD, Department of Thoracic-Head & Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses efficacy findings from the phase 1b/2 KontRASt-01 trial (NCT04699188) in patients with KRAS G12C–mutated solid tumors.

At the 2023 IASLC World Conference on Lung Cancer, Negrao presented preliminary findings from the KontRASt-01 trial, which was a dose-escalation and dose-expansion trial evaluating the KRAS G12C inhibitor JDQ443 as monotherapy and in combination with the SHP2 inhibitor TNO155 in patients with solid tumors, including non–small cell lung cancer (NSCLC), harboring KRAS G12C mutations. The primary end points of the dose-escalation portion of the trial were safety, tolerability, and recommended doses and regimens for future studies. The primary end point of the dose-expansion portion of this trial was overall response rate (ORR). Eligible patients included adults who had previously received standard-of-care therapy and had an ECOG performance status of 0 or 1. Patients in the dose-escalation group and some patients in the dose-expansion groups could have received prior treatment with KRAS G12C inhibitors.

As of February 1, 2023, 50 patients with solid tumors had received the combination in a dose-escalation cohort. In total, 48.0% of the patients enrolled in this trial had NSCLC, and 17 patients in the overall population had received prior KRAS G12C inhibitors.

Treatment with JDQ443 plus TNO155 led to responses in both KRAS G12C inhibitor–naïve and KRAS G12C inhibitor–pretreated patients with NSCLC, Negrao says, adding that the confirmed ORR was 33.3% (95% CI, 12.3%-60.9%) in both patient subgroups. Furthermore, the disease control rates were 66.7% (95% CI, 39.1%-87.7%) and 83.3% (95% CI, 56.2%-97.0%) in the KRAS G12C inhibitor–pretreated and –naïve populations, respectively, Negrao explains. Responses were durable in both cohorts, and some patients achieved responses lasting more than 6 months, Negrao emphasizes. In addition, some patients remained on the trial for at least 1 year, Negrao concludes.