Respiratory and mediastinal neoplasms malignant and unspecified, Miscellaneous and site unspecified neoplasms malignant and unspecified Solid tumor
Conditions
Interventions
BDTX-189 will be supplied as 25-mg, 50-mg, 100-mg, and 200-mg tablets. Higher
tablet dose strengths may be made available during the dose-escalation phase.
The starting dose is 25 mg BDTX-189 PO QD.
Sponsors
Black Diamond Therapeutics, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Histologically- or cytologically-confirmed locally advanced or metastatic solid tumor with documented recurrence or disease progression from standard anticancer therapy in the advanced/metastatic setting; No standard therapy available or standard therapy is considered unsuitable or intolerable according to the Investigator and consultation with the Medical Monitor; Patients with a solid tumor harboring an: a. Allosteric HER2 mutation b. EGFR or HER2 exon 20 insertion mutation as determined by a validated next-generation sequencing (NGS) test routinely used by each institution using tissue and/or plasma. Eligible mutations are summarized in Appendix I. Eligible patients will be assigned to one of the 4 following cohorts: Cohort 1: NSCLC with EGFR or HER2 exon 20 insertion mutation Cohort 2: Breast cancer with an allosteric HER2 mutation and EGFR/HER2 exon 20 insertion mutations Cohort 3: Any tumor (except breast) with an S310F/Y mutation Cohort 4: Any other allosteric HER2 mutation and EGFR/HER2 exon 20 insertion mutations not assigned to Cohorts 1-3; Adequate archival tumor tissue or willing to undergo pretreatment biopsy; Measurable disease according to RECIST version 1.1.
Exclusion criteria
Exclusion criteria: Clinical laboratory values meeting the following criteria within 4 weeks (28 days) prior to baseline: a. Serum creatinine >=1.5 × upper limit of normal (ULN) or calculated creatinine clearance =1.5 × ULN or >=3.0 × ULN in the presence of documented Gilbert*s syndrome c. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=2.5 × ULN, or AST or ALT >=5.0 × ULN in the presence of liver metastases d. Hematologic function: i. Absolute neutrophil count (ANC) =24 weeks by RECIST v1.1) to approved or investigational HER2 or EGFR therapies (e.g., afatinib, lapatinib, dacomitinib, neratinib, trastuzumab deruxtecan, poziotinib, mobocertinib, amivantamab) a. Patients with or without tumor response discontinuing after 8 weeks or less of therapy due to toxicity may be considered after discussion with the Sponsor Medical Monitor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Confirmed objective response rate (ORR) defined as either a complete response (CR) or partial response (PR) by RECIST version 1.1 as determined by the Investigator based on computed tomography (CT) or magnetic resonance imaging (MRI) scans | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of TEAEs; changes in clinical laboratory parameters, vital signs, and electrocardiogram (ECG) parameters, cardiac function; and physical examination results PopPK parameters oral clearance (Cl/F), oral volume of distribution (Vd/F), and first-order absorption rate constant (Ka) for BDTX-189. Cl/F will be used to generate estimates of BDTX-189 area under the concentration time curve (AUC). Possible PK/safety, PK/efficacy correlations, and covariate analysis of intrinsic/extrinsic factors. Additional measures of antitumor activity including DOR, DCR, PFS, and OS. | — |
Countries
Netherlands
Outcome results
None listed