Phase 1/2 Study of BDTX-1535 in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1/2 Study to Assess BDTX-1535, an Oral EGFR Inhibitor, in Patients With Glioblastoma or Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05256290
• Other study ID #: BDTX-1535-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 31, 2022
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: Black Diamond Therapeutics, Inc.
• Contact: BDTX Clinical Trial Navigation Service
• Phone: (866) 955-4397
• Email: blackdiamondtx[@]careboxhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), optimal dosage, central nervous system (CNS) activity, and antitumor activity of BDTX-1535. The study population comprises adults with either advanced/metastatic non-small cell lung cancer (NSCLC) with non-classical or acquired epidermal growth factor receptor (EGFR) resistance (EGFR C797S) mutations with or without CNS disease (in Phase 1 and Phase 2), or glioblastoma multiforme (GBM) expressing EGFR alterations (Phase 1 only). All patients will self administer BDTX-1535 monotherapy by mouth in 21-day cycles. Phase 1 enrollment is now complete. Phase 2 is currently enrolling.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Phase 2 Eligibility:

Key Inclusion Criteria Required for locally advanced or metastatic NSCLC:

• Measurable disease by RECIST 1.1 criteria.
• Adequate bone marrow or organ function.
• Life expectancy of = 3 months.
• Sufficient performance status.
• Confirmed NSCLC, without small cell lung cancer transformation with or without brain metastases.
• Disease progression following or intolerance of standard of care (excluding patients

in the treatment-naïve non-classical driver cohort):

• Cohort 1 (Non-Classical driver cohort): Advanced/metastatic NSCLC with a non-classical driver EGFR mutation (eg, G719X) following up to 2 lines of therapy with only 1 prior EGFR TKI regimen (third-generation preferred; other approved EGFR TKI acceptable).
• Cohort 2 (Acquired resistance C797S cohort): Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only one EGFR TKI, which must be a third generation EGFR TKI (eg, osimertinib).
• Cohort 3 (First-line non-classical driver cohort): Treatment-naïve advanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle of chemotherapy or immune checkpoint inhibitor are permitted).
• Identification of one (or more) of the following EGFR mutations by Next Generation Sequencing (NGS) as determined by a local assay performed in a validated laboratory in

the absence of other known resistance mutations (eg, T790M, MET):

• Non-classical driver EGFR mutations (eg, L861R, S768I, G719X).
• EGFR acquired resistance mutation (eg, C797S) to a 3rd generation EGFR TKI.
• NGS test must be obtained after progression on the most recent therapy; at the time of diagnosis for the patients in Cohort 3 only.

Key Exclusion Criteria:

• Known resistant mutations in tumor tissue or by liquid biopsy (eg, T790M, MET).
• Received more than 1 EGFR TKI therapy (ie, erlotinib or gefitinib) for the treatment of metastatic or recurrent EGFR NSCLC.
• Any history of interstitial lung disease related to EGFR TKI use.
• Symptomatic or radiographic leptomeningeal disease.
• Symptomatic brain metastases or spinal cord compression requiring urgent clinical intervention.
• Unresolved toxicity from prior therapy.
• Significant cardiovascular disease.
• Major surgery within 4 weeks of study entry or planned during study.
• Ongoing or recent anticancer therapy or radiation therapy.
• Evidence of malignancy (other than study-specific malignancies) requiring active therapy within the next 2 years.
• Active hepatitis B or C infection and/or known human immunodeficiency virus (HIV) carrier.
• Poorly controlled gastrointestinal disorders.

Related Conditions & MeSH terms

• Advanced Lung Carcinoma
• Advanced Non-Small Cell Squamous Lung Cancer
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• EGF-R Positive Non-Small Cell Lung Cancer
• EGFR-TKI Resistant Mutation
• Glioblastoma
• Lung Neoplasms
• Metastatic Lung Cancer
• Metastatic Lung Non-Small Cell Carcinoma
• Non-Small Cell Lung Cancer
• NSCLC

Intervention

Drug:
• BDTX-1535 monotherapy
BDTX-1535 is a 4th generation irreversible brain penetrant EGFR MasterKey inhibitor, which targets a family of oncogenic EGFR classical and non-classical driver and resistance mutations in NSCLC.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical	Seoul
Korea, Republic of	National Cancer Center	Seoul
Korea, Republic of	Samsung Comprehensive Cancer Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	University of Alabama	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	HealthOne Denver	Denver	Colorado
United States	City of Hope Comprehensive Cancer Center (Duarte Campus)	Duarte	California
United States	Next Ocology	Fairfax	Virginia
United States	Prisma Health	Greenville	South Carolina
United States	City of Hope Huntington Beach	Huntington Beach	California
United States	City of Hope Orange County Lennar Foundation Cancer Center	Irvine	California
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Baptist Health Miami	Miami	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University/Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	Siteman Cancer Center	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Center/University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Black Diamond Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Dose Escalation: To determine the maximum tolerated dose (MTD), if one exists, and the preliminary recommended Phase 2 dose(s) (RP2D[s]) of BDTX-1535	Dose-limiting toxicities (DLTs) in Cycle 1	The first treatment 21-day cycle (Cycle 1)
Primary	Phase 2: To assess antitumor efficacy of BDTX-1535	Objective response rate (ORR) as assessed by Investigator using RECIST version 1.1	Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs)		Through study completion, approximately 1 year
Secondary	Phase 1 and Phase 2: To characterize the plasma concentration of BDTX-1535 following single and multiple dosing		Cycle 1 Days 1, 2, 15, and 16, Cycles 2 to 5 Day 1, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 1: To assess the preliminary antitumor activity of BDTX-1535 by objective response as assessed by RECIST version 1.1 (for patients with NSCLC) or Response Assessment in Neuro-oncology (RANO) (for patients with GBM)		Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 1: To assess the effect of tablet formulation on the plasma concentration of BDTX-1535		Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days)
Secondary	Phase 1: To assess the effect of food on the plasma concentration of BDTX-1535		Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days)
Secondary	Phase 2: To assess duration of tumor response by RECIST version 1.1		Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 2: To assess progression free survival by RECIST version 1.1		Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 2: To evaluate CNS ORR by RANO for brain metastases criteria (RANO-BM)		Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 2: To assess NSCLC disease-related symptoms and change of symptoms with BDTX-1535 treatment	Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ); Verbal rating scale used (for example: Never/Rarely/Sometimes/Often/Always)	At select timepoints: Cycle 1 Day, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, and at study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 2: To assess treatment related side effects with BDTX-1535	National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (NCI-PRO-CTCAE) Survey: Rating scale used (for example never/rarely/occasionally/frequently/almost constantly)	At select timepoints: Cycle 1 Day, Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, and at study completion, approximately 1 year (each cycle is 21 days)
Secondary	Phase 2: To determine the optimal dosage of BDTX-1535 (100 mg or 200 mg daily dose)		At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2