NEW YORK – Black Diamond Therapeutics said on Tuesday that, following encouraging initial Phase I data for BDTX-1535 in EGFR-mutated non-small cell lung cancer, it plans to discuss the path to approval and Phase II trial strategy with the US Food and Drug Administration.
In a dose-escalation portion of the ongoing Phase I trial, BDTX-1535 demonstrated clinical proof of activity, including tumor responses and circulating tumor DNA changes, in NSCLC patients whose cancers harbored both acquired resistance EGFR mutations and intrinsic driver EGFR mutations.
In the Phase I study, Black Diamond is evaluating BDTX-1535 in patients with either advanced or metastatic NSCLC harboring EGFR mutations or in patients with recurrent glioblastoma multiforme expressing EGFR alterations.
After the dose-escalation portion of the trial, the firm has designed the trial to branch into several disease-specific expansion cohorts to assess further endpoints.
In the initial dose-escalation portion of the Phase I trial, 24 patients with recurrent EGFR-mutated NSCLC — both with or without central nervous system metastases — and 27 patients with recurrent glioblastoma with EGFR alterations received BDTX-1535 in different dose levels. The NSCLC patients had received a median of two prior therapies, including an EGFR inhibitor, which, in most cases, was AstraZeneca's third-generation EGFR TKI Tagrisso (osimertinib). The glioblastoma patients had received surgery, radiation, and chemotherapy.
As of June 16, five out of 12 NSCLC patients had a radiographic confirmed partial response, one patient had an unconfirmed partial response, and six patients had stable disease. The patients with confirmed partial responses had a range of EGFR mutations including acquired C797S resistance mutations as well as classical, intrinsic, and acquired resistance mutations. Two NSCLC patients had confirmed improvements in central nervous system metastases. The drug was tolerable with no new safety signals.
In the update on Tuesday, Black Diamond only shared preliminary data on the NSCLC patients. According to the firm, it plans to provide an update on the glioblastoma patients during the fourth quarter of 2023.
Following these response data, Black Diamond plans to begin two expansion cohorts using the 200 mg per day dosage for NSCLC patients with acquired resistance or intrinsic driver EGFR mutations who received up to two prior treatments including a third-generation EGFR TKI. After Black Diamond meets to discuss the dose-escalation data with the FDA, the firm said it may evaluate additional doses.
In the expansion cohorts, investigators will measure overall response rates and durability of response, which Black Diamond hopes will help pave the way for an accelerated approval path for EGFR-mutated NSCLC. Following the late-2023 FDA discussion, the firm also plans to open another expansion cohort that includes treatment-naïve NSCLC patients whose tumors harbor intrinsic driver mutations.
"These initial safety and clinical activity data support the continued development of BDTX-1535 as a potential first and best-in-class treatment option for osimertinib-resistant NSCLC patients," Black Diamond Chief Medical Officer Sergey Yurasov said in a statement. "Importantly, BDTX-1535 is the first EGFR TKI to show radiographic responses across NSCLC patients whose cancers are driven by diverse mutation families including acquired resistance mutations after osimertinib therapy, as well as in patients whose cancers are driven by classical and intrinsic driver mutations, providing clinical validation for our MasterKey approach of targeting families of mutations with a single drug."
Shares of Black Diamond Therapeutics jumped more than 200 percent following the news to $5.93 in Tuesday afternoon trading on the Nasdaq.