Patient Receives Treatment With Novel Drug in First-in-Human Trial Assessing its Safety and Efficacy in Brain and Lung Cancer

The drug, known as BDTX-1535, is being investigated in patients with glioblastoma that harbors EGFR alterations and non-small cell lung cancer that harbors EGFR mutations of intrinsic or acquired resistance and disease that has failed standard treatment.

The first patient has received treatment with BDTX-1535 in an early-phase trial assessing the novel drug’s safety and efficacy in patients with non-small cell lung cancer or glioblastoma, an aggressive type of brain cancer, according to the agent’s manufacturer, Black Diamond Therapeutics.

“The dosing of the first patient in our phase 1 study of BDTX-1535, a next-generation brain-penetrant inhibitor of oncogenic EGFR MasterKey mutations is an important step as we believe this program is uniquely positioned to address the existing unmet needs of EGFR-mutant (non-small cell lung cancer) and (glioblastoma),” David M. Epstein, CEO of Black Diamond Therapeutics, said in the press release.

The plan for the phase 1 study is to enroll approximately 90 patients and assess the safety, tolerability and preliminary efficacy of treatment with BDTX-1535 in glioblastoma that harbors EGFR alterations and non-small cell lung cancer that harbors EGFR mutations of intrinsic or acquired resistance and disease that has failed standard treatment.

The study authors plan to include cohorts of patients receiving escalating doses of study drug to identify a recommended dose for the phase 2 portion of the study.

All enrolled patients must be aged 18 years or older and have adequate bone marrow or organ function.

Any patient will be excluded from enrollment if they have known resistant mutations such as EGFR T790M, EGFR exon 20 insertion mutations, MET (including MET amplification), KRAS or HER2 (C805S, T798I, or T862A). Patients with glioblastoma who were previously treated with an EGFR inhibitor will also be excluded from the trial.

Of note, BDTX-1535 is an oral drug that is an irreversible inhibitor of EGFR alterations, which means that it may block certain enzymes that the cancer cells need to grow.

“Despite recent successes in targeting EGFR-mutated (non-small cell lung cancer), there is still a need for better therapeutics for patients with disease progression following first-line EGFR inhibitors,” Dr. Melissa Johnson, director of Lung Cancer Research for Sarah Cannon Research Institute at Tennessee Oncology in Nashville, said in the release. “We hope to assess the ability of BDTX-1535 to inhibit tumors with primary TKI-resistant EGFR mutations or those with on-target acquired resistance mutations.”

Approximately half of glioblastoma tumors, according to the release, express one or more co-occurring EGFR mutations. The release continued, noting that there are no precision drugs that are Food and Drug Administration-approved to treat this patient population.

“(Glioblastoma) is an aggressive form of brain cancer with limited treatment options,” Dr. Patrick Y. Wen, director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute in Boston, said in the release. “A majority of (glioblastoma) tumors will co-express EGFR alterations, including mutations, splice variants and amplification, making EGFR an attractive target for new therapies with (central nervous system) penetration and potency against the spectrum of co-expressed EGFR alterations.”

The trial is expected to be completed by September 2024.

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