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 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 

 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 

 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 

 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.

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Salman R. Punekar, MD discusses the rationale for evaluating safety and preliminary anti-tumor activity of NT-112 in solid tumors with the KRAS G12D mutation.

Dr Punekar on the Importance of Complete Biomarker Testing in Lung Cancer

Salman R. Punekar, MD, oncologist, NYU Langone’s Perlmutter Cancer Center, assistant professor, Department of medicine, NYU Grossman School of Medicine, discusses the importance of performing complete biomarker testing in non–small cell lung cancer (NSCLC), highlighting current and emerging biomarkers under investigation in this space.

In recent years, there has been a significant shift towards the use of complete biomarker testing in cancer care, Punekar begins. This is a departure from the previously limited approach of short panel testing, he says. Short panel testing, which focused on a limited number of genes, restricted the ability to identify all potential mutations associated with different treatment options, thereby limiting the benefit seen in patient outcomes, Punekar explains.

Key biomarkers in lung cancer can be broadly categorized into 2 types: prognostic and actionable, Punekar continues. Identifying prognostic biomarkers, such as 

, can provide insights into the aggressiveness of disease or development of resistance, but may not have immediate treatment implications, Punekar states. Conversely, actionable biomarkers, also known as driver mutations or alterations, can directly inform treatment decision making. Examples in NSCLC include E

 mutations, which have available targeted therapies available, he adds.

 are gaining attention in NSCLC research, Punekar notes. Although these biomarkers may be less common, they may have associated targeted therapies currently under evaluation in clinical trials, he says.

Overall, the shift towards comprehensive biomarker testing allows for a more personalized approach to cancer treatment, enabling clinicians to identify actionable mutations and match patients with more effective targeted therapies, Punekar emphasizes. As more biomarkers are discovered and validated, ongoing research and clinical trials continue to explore their potential in improving patient outcomes.

Salman R. Punekar, MD, discusses the importance of complete biomarker testing and the landscape of biomarkers in lung cancer.

Salman R. Punekar, MD

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

Dr Punekar on the Importance of Complete Biomarker Testing in Lung Cancer