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

• ClinicalTrials.gov Identifier: NCT05256290
• Recruitment Status: Recruiting
• First Posted: February 25, 2022
• Last Update Posted: March 6, 2024
• Sponsor: Black Diamond Therapeutics, Inc.
• Information provided by (Responsible Party): Black Diamond Therapeutics, Inc.

Tracking Information

• First Submitted Date: February 15, 2022
• First Posted Date: February 25, 2022
• Last Update Posted Date: March 6, 2024
• Actual Study Start Date: March 31, 2022
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 3, 2024)

• 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 [ Time Frame: The first treatment 21-day cycle (Cycle 1) ]
  Dose-limiting toxicities (DLTs) in Cycle 1
• Phase 2: To assess antitumor efficacy of BDTX-1535 [ Time Frame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
  Objective response rate (ORR) as assessed by Investigator using RECIST version 1.1

Original Primary Outcome Measures (submitted: February 24, 2022)

Number of participants with dose limiting toxicities (DLTs) [ Time Frame: From first dose of study treatment until the end of Cycle 1 (approximately 21 days) ]

DLTs are based on drug-related adverse events, including pre-defined hematological and non-hematological toxicities, that occur from the first dose of study treatment through the end of Cycle 1

Current Secondary Outcome Measures (submitted: January 3, 2024)

• Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, approximately 1 year ]
• Phase 1 and Phase 2: To characterize the plasma concentration of BDTX-1535 following single and multiple dosing [ Time Frame: 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) ]
• 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) [ Time Frame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
• Phase 1: To assess the effect of tablet formulation on the plasma concentration of BDTX-1535 [ Time Frame: 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) ]
• Phase 1: To assess the effect of food on the plasma concentration of BDTX-1535 [ Time Frame: 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) ]
• Phase 2: To assess duration of tumor response by RECIST version 1.1 [ Time Frame: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
• Phase 2: To assess progression free survival by RECIST version 1.1 [ Time Frame: Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
• Phase 2: To evaluate CNS ORR by RANO for brain metastases criteria (RANO-BM) [ Time Frame: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days) ]
• Phase 2: To assess NSCLC disease-related symptoms and change of symptoms with BDTX-1535 treatment [ Time Frame: 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) ]
  Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ); Verbal rating scale used (for example: Never/Rarely/Sometimes/Often/Always)
• Phase 2: To assess treatment related side effects with BDTX-1535 [ Time Frame: 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) ]
  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)
• Phase 2: To determine the optimal dosage of BDTX-1535 (100 mg or 200 mg daily dose) [ Time Frame: At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2 ]

Original Secondary Outcome Measures (submitted: February 24, 2022)

• Number of participants with treatment-emergent adverse events [ Time Frame: Up to approximately 3 years ]
  An AE is any untoward medical occurrence in a participant who receives study treatment, which does not necessarily have a causal relationship with the treatment
• Maximum plasma concentration (Cmax) of BDTX-1535 [ Time Frame: Up to approximately 3 years ]
  Cmax is calculated to characterize the pharmacokinetic properties of study treatment
• Time to maximum plasma concentration (Tmax) of BDTX-1535 [ Time Frame: Up to approximately 3 years ]
  Tmax is calculated to characterize the pharmacokinetic properties of study treatment
• Area under the plasma concentration-time curve (AUC) of BDTX-1535 [ Time Frame: Up to approximately 3 years ]
  AUC is calculated to characterize the pharmacokinetic properties of study treatment
• Objective Response Rate (ORR) [ Time Frame: Up to approximately 3 years ]
  ORR is the percentage of participants who achieve a complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) criteria
• Duration of Response (DOR) [ Time Frame: Up to approximately 3 years ]
  DOR is the time from initial tumor response of CR or PR to first documentation of progressive disease (PD) or death due to any cause, whichever occurs first
• Disease Control Rate (DCR) [ Time Frame: Up to approximately 3 years ]
  DCR is the percentage of participants who achieve a CR, PR or stable disease
• Progression-Free Survival (PFS) [ Time Frame: Up to approximately 3 years ]
  PFS is the time from start of study treatment to PD or death due to any cause, whichever occurs first

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer
• Advanced Non-Small Cell Squamous Lung Cancer
• Metastatic Lung Non-Small Cell Carcinoma
• Metastatic Lung Cancer
• NSCLC
• Advanced Lung Carcinoma
• Epidermal Growth Factor Receptor C797S
• Epidermal Growth Factor Receptor G719X
• EGF-R Positive Non-Small Cell Lung Cancer
• EGFR-TKI Resistant Mutation

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.

Study Arms

• Experimental: Phase 1 Dose Escalation - Monotherapy (Recruitment Closed)
  • Advanced/metastatic NSCLC with acquired resistance EGFR mutation (eg, C797S), following a 3rd generation EGFR inhibitor in the 1st line setting (in the absence of concurrent T790M).
  • Advanced/metastatic NSCLC with non-classical EGFR mutation (eg, G719X) following standard-of-care therapy with an EGFR inhibitor
  • Recurrent GBM with confirmed EGFR alterations (including amplification, mutation, and/or variant)
  Intervention: Drug: BDTX-1535 monotherapy
• Experimental: Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver Mutations
  Advanced/metastatic NSCLC with a non-classical driver EGFR mutation following up to 2 lines of therapy with only 1 prior EGFR targeted regimen (third-generation preferred; other approved EGFR inhibitors acceptable)
  Intervention: Drug: BDTX-1535 monotherapy
• Experimental: Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation
  Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only 1 EGFR targeted regimen, which must be a third generation EGFR TKI (eg, osimertinib)
  Intervention: Drug: BDTX-1535 monotherapy
• Experimental: Phase 2 Cohort 3: Treatment Naive NSCLC EGFR Non-Classical Driver Mutations
  Treatment-naïve (first-line) advanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle of chemotherapy or immune checkpoint inhibitor are permitted)
  Intervention: Drug: BDTX-1535 monotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 3, 2024): 200
• Original Estimated Enrollment (submitted: February 24, 2022): 90
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BDTX Clinical Trial Navigation Service; (866) 955-4397; blackdiamondtx@careboxhealth.com

• Listed Location Countries: Korea, Republic of, United States

Administrative Information

• NCT Number: NCT05256290
• Other Study ID Numbers: BDTX-1535-101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Black Diamond Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Black Diamond Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Black Diamond Therapeutics; Black Diamond Therapeutics

• PRS Account: Black Diamond Therapeutics, Inc.
• Verification Date: March 2024