Dr Punekar on the Evaluation of NT-112 in KRAS G12D+ Advanced Solid Tumors

Salman R. Punekar, MD, oncologist, New York University (NYU) Langone’s Perlmutter Cancer Center, assistant professor, Department of Medicine, NYU Grossman School of Medicine, discusses the rationale and design behind an open-label, phase 1, multicenter study (NCT06218914) evaluating the safety and preliminary antitumor activity of NT-112 in patients who are human leukocyte antigen (HLA)-C*08:02 positive and have unresectable, locally advanced or metastatic solid tumors harboring KRAS G12D mutations.

KRAS mutations are prevalent across multiple cancer types, notably pancreatic, lung, and colorectal (CRC) cancers, Punekar beings. Although KRAS G12C inhibitors have received regulatory approval in lung cancer and CRC, there are no FDA-approved targeted therapies for patients with tumors harboring KRAS G12D mutations, creating a significant therapeutic gap, Punekar explains. NT-112 is an autologous T-cell receptor (TCR) T-cell therapy specifically designed to target KRAS G12D mutations presented by HLA-C*08:02 on cells in the tumor microenvironment or lymphatic organs, he continues.

The first-in-human, open-label, multicenter, phase 1, dose-escalation study will enroll up to 24 adult patients who are HLA-C*08:02 positive and have unresectable, locally advanced or metastatic non–small cell lung cancer, CRC, pancreatic adenocarcinoma, endometrial cancer, or any other solid tumor harboring a KRAS G12D mutation. At least 1 prior line of standard-of-care treatment is required. Enrolled patients will undergo leukapheresis, from which CD4- and CD8-positive T cells will be enriched and activated ex vivo. After seven days of lymphodepletion, patients will receive a single infusion of NT-112 plus 300,000 IU/kg of recombinant interleukin-2 per day for up to 8 days.

The primary objective of this phase 1 trial is to assess the safety and tolerability of NT-112, and to determine the maximum tolerated dose and recommended phase 2 dose. Evaluating the preliminary antitumor activity of NT-112 is a secondary end point. The phase 1 study is active and enrolling, and the first patient was expected to be dosed in June 2024.