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

March 5, 2024 updated by: Black Diamond Therapeutics, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

BDTX-1535 is an orally available, highly potent, selective, irreversible inhibitor of allosteric epidermal growth factor receptor (EGFR) alterations, including amplification, mutations, and splice variants which have been identified in glioblastoma (GBM) and mutations in non-small cell lung cancer (NSCLC) associated with intrinsic or acquired resistance. The open label, multicenter will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of BDTX-1535 in patients with GBM harboring EGFR alterations and NSCLC with EGFR mutations of intrinsic or acquired resistance who have failed standard treatment. Dose escalation cohorts will be used to determine the maximum tolerated dose and recommended phase 2 dose of BDTX-1535 oral administration

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Comprehensive Cancer Center
        • Contact:
      • Seoul, Korea, Republic of, 05505
      • Seoul, Korea, Republic of, 10408
        • Recruiting
        • National Cancer Center
        • Contact:
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
    • California
      • Beverly Hills, California, United States, 90211
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center (Duarte Campus)
        • Contact:
        • Contact:
          • Phone Number: 626-218-1133
      • Huntington Beach, California, United States, 92648
        • Recruiting
        • City of Hope Huntington Beach
        • Contact:
        • Contact:
          • Phone Number: 626-218-1133
      • Irvine, California, United States, 92618
        • Recruiting
        • City of Hope Orange County Lennar Foundation Cancer Center
        • Contact:
        • Contact:
          • Phone Number: 626-218-1133
      • Los Angeles, California, United States, 90067
    • Colorado
    • Florida
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Cancer Center
        • Contact:
        • Contact:
    • Massachusetts
    • Missouri
    • New York
      • Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center
        • Contact:
      • New York, New York, United States, 10021
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Contact:
          • Nathan Pennell, MD, PhD
          • Phone Number: 216-445-9282
          • Email: penneln@ccf.org
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University/Sidney Kimmel Cancer Center
        • Contact:
    • South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37203
    • Texas
    • Virginia
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center/University of Washington
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)
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.
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)
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.
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)
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.
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)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
The first treatment 21-day cycle (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
Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame: Through study completion, approximately 1 year
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Black Diamond Therapeutics, Inc.

Investigators

  • Study Director: Black Diamond Therapeutics, Black Diamond Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 31, 2022

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

February 15, 2022

First Submitted That Met QC Criteria

February 24, 2022

First Posted (Actual)

February 25, 2022

Study Record Updates

Last Update Posted (Estimated)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BDTX-1535-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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