Solid Tumor
Conditions
Keywords
solid tumor, HER2 mutation, exon 20 insertion mutation, HER2 positive, Genes, HER2, Genes, erbb2, HER2 amplification, HER2 overexpression, genes, exon 20 insertion, lung cancer, non-small cell lung cancer, breast cancer, colon cancer, colorectal cancer, bladder cancer, endometrial cancer, gastric cancer, biliary tract cancer
Brief summary
This was a clinical study with an orally administered drug, BDTX-189 in participants with advanced solid tumors that had select mutations or alterations in human epidermal growth factor receptor 2 (HER2/ErbB2) genes or epidermal growth factor receptor (EGFR/ErbB1). The main goals of this study were to: * Find the recommended dose of BDTX-189 that can be given safely to participants * Learn more about the side effects of BDTX-189 * Learn what the body does to BDTX-189 after it has been taken (pharmacokinetics or PK) * Determine the preliminary antitumor activity of BDTX-189 in participants with select allosteric ErbB gene mutations
Detailed description
BDTX-189 is an irreversible, small molecular inhibitor that is highly selective versus wild-type EGFR and potent for cancer driver mutations of the ErbB family, including extracellular, transmembrane, and kinase domain allosteric mutations of HER2, as well as EGFR and HER2 exon 20 insertion mutations. These allosteric ErbB mutations are found in 1 - 2 % of most solid tumors and enriched in some cancers with a prevalence of about 2 - 7% such as in non-small cell lung cancer, breast cancer, colorectal cancer, bladder cancer, and endometrial cancer. Currently approved HER2 and EGFR directed therapies are not active against the spectrum of allosteric mutations at relevant and tolerated exposure levels. This Phase 1/2 multi-center, open-label trial was a first-in-human study that evaluated BDTX-189 orally administered daily as a single agent in patients with solid tumors harboring select mutations or alterations. The Phase 1 portion was a dose escalation primarily designed to assess the safety and tolerability of BDTX-189 and to determine a recommended Phase 2 dose (RP2D). Phase 1 focused on patients with a solid tumor and with alterations such as: * Allosteric HER2 or HER3 mutation(s) * EGFR or HER2 exon 20 insertion mutation(s) * HER2 amplified or overexpressing tumors * EGFR exon 19 deletion or L858R mutation Eligible mutations must have been determined by a validated next-generation sequencing (NGS) test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory. The Phase 2 portion was not initiated.
Interventions
DRUGBDTX-189
Participants received a daily, oral dose of BDTX-189 as part of a 3 week cycle.
Sponsors
Black Diamond Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main 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 Phase 1 Only: * Solid tumor patients with alterations that may be associated with antitumor activity based on preclinical data for BDTX-189 such as: 1. Allosteric HER2 or HER3 mutation(s) 2. EGFR or HER2 exon 20 insertion mutation(s) 3. HER2 amplified or overexpressing tumors 4. EGFR exon 19 deletion or L858R mutation Eligible mutations must be determined by a validated next-generation sequencing (NGS) test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory. * Adequate archival tumor tissue or willing to undergo pretreatment biopsy * Measurable disease according to RECIST version 1.1 Main
Exclusion criteria
* Clinical laboratory values meeting the following criteria within 4 weeks (28 days) prior to baseline: 1. Serum creatinine ≥1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≤60 mL/min using Cockcroft-Gault equation 2. Total bilirubin ≥1.5 × ULN or ≥3.0 × ULN in the presence of documented Gilbert's syndrome 3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 × ULN, or AST or ALT ≥5.0 × ULN in the presence of liver metastases 4. Hematologic function: 1. Absolute neutrophil count (ANC) ≤1000 cells/μL 2. Hemoglobin ≤8.5 g/dL or 5.28 mmol/L 3. Platelet count ≤75,000/μL * Significant cardiovascular disease, including: 1. Cardiac failure New York Heart Association Class III or IV, or left ventricular ejection fraction (LVEF) \<50% or below the lower limit of the Institution's normal range 2. Myocardial infarction, severe or unstable angina within 6 months prior to baseline 3. Significant thrombotic or embolic events within 3 months prior to baseline 4. History or presence of any uncontrolled cardiovascular disease 5. Personal or family history of long QT syndrome * ECG findings meeting any of the following criteria: 1. Evidence of second- or third-degree atrioventricular block 2. Clinically significant arrhythmia (as determined by the Investigator) 3. QTcF interval of \>470 msec * Leptomeningeal or untreated and/or symptomatic CNS malignancies (primary or metastatic) * Women who are pregnant or breast-feeding * Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline * Known concurrent KRAS mutation * Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S mutation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | After the first dose of treatment for up to 21 days. | Certain toxicities will be considered dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | From Cycle 1 Day 1 (each cycle is 21 days) until 30 days post last dose | Adverse events will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
| Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | Multiple time points during Cycles 1-4 (each cycle is 21 days) | Blood samples will be taken to measure the plasma concentrations of BDTX-189 in both a fed and fasted state. |
| Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Assessed until disease progression or death for up to 12 months | Objective response is defined as the proportion of participants who achieved a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1. |
| Phase 1: Progression-free Survival as a Measure of Antitumor Activity | Assessed until disease progression or death for up to 12 months | Progression-free survival is the time from first study dose until disease progression (PD; target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions) per RECIST v1.1. |
Countries
Denmark, France, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation 25 mg QD Patients who received doses at 25 mg once daily under fasted conditions. | 1 |
| Dose Escalation 50 mg QD Patients who received doses at 50 mg once daily under fasted conditions. | 1 |
| Dose Escalation 100 mg QD Patients who received doses at 100 mg once daily under fasted conditions. | 1 |
| Dose Escalation 200 mg QD Patients who received doses at 200 mg once daily under fasted conditions. | 2 |
| Dose Escalation 400 mg QD Patients who received 400 mg once daily under fasted conditions. | 10 |
| Dose Escalation 800 mg QD Patients who received 800 mg once daily under fasted conditions. | 18 |
| Dose Escalation 800 mg QD NF Patients who received 800 mg once daily under not fasted conditions. | 13 |
| Dose Escalation 1000 mg QD Patients who received 1000 mg once daily under not fasted conditions | 7 |
| Dose Escalation 1200 mg QD Patients who received 1200 mg once daily under fasted conditions. | 6 |
| Dose Escalation 400 mg BID Patients who received 400 mg twice daily under not fasted conditions. | 4 |
| Dose Escalation 600 mg BID Patients who received 600 mg twice daily under not fasted conditions. | 6 |
| Dose Escalation 800 mg BID Patients who received 800 mg twice daily under fasted conditions. | 5 |
| Safety Expansion 800 mg QD Patients in safety expansion who received 800 mg once daily under not fasted conditions. | 17 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 2 | 1 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 2 | 7 | 2 | 2 | 1 | 1 | 1 | 0 | 10 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 0 | 0 | 1 | 2 | 8 | 5 | 3 | 4 | 1 | 3 | 2 | 1 | 0 |
| Overall Study | Started new therapy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study terminated early by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 1 | 0 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Dose Escalation 50 mg QD | Dose Escalation 100 mg QD | Dose Escalation 200 mg QD | Dose Escalation 400 mg QD | Dose Escalation 800 mg QD | Dose Escalation 800 mg QD NF | Dose Escalation 1000 mg QD | Dose Escalation 25 mg QD | Dose Escalation 1200 mg QD | Dose Escalation 400 mg BID | Dose Escalation 600 mg BID | Dose Escalation 800 mg BID | Safety Expansion 800 mg QD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 6 Participants | 9 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 4 Participants | 2 Participants | 0 Participants | 10 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 9 Participants | 10 Participants | 4 Participants | 1 Participants | 6 Participants | 0 Participants | 4 Participants | 5 Participants | 7 Participants | 52 Participants |
| Age, Continuous | 65 years | 51 years | 60 years STANDARD_DEVIATION 17 | 64.5 years STANDARD_DEVIATION 9.48 | 65.4 years STANDARD_DEVIATION 11.94 | 60.2 years STANDARD_DEVIATION 7 | 61.4 years STANDARD_DEVIATION 7 | 56 years | 55.8 years STANDARD_DEVIATION 6.59 | 71.0 years STANDARD_DEVIATION 6.06 | 59.3 years STANDARD_DEVIATION 11.99 | 58.0 years STANDARD_DEVIATION 5.7 | 65.3 years STANDARD_DEVIATION 10.34 | 63.1 years STANDARD_DEVIATION 10.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 9 Participants | 15 Participants | 11 Participants | 6 Participants | 1 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 11 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 5 participants | 5 participants |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants | 10 participants | 18 participants | 13 participants | 7 participants | 1 participants | 6 participants | 4 participants | 6 participants | 5 participants | 12 participants | 86 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 5 Participants | 9 Participants | 9 Participants | 4 Participants | 0 Participants | 6 Participants | 3 Participants | 5 Participants | 3 Participants | 8 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 9 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 9 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 0 / 1 | 0 / 1 | 0 / 2 | 2 / 10 | 7 / 18 | 2 / 13 | 2 / 7 | 1 / 6 | 1 / 4 | 1 / 6 | 0 / 5 | 10 / 17 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 2 / 2 | 10 / 10 | 18 / 18 | 13 / 13 | 7 / 7 | 6 / 6 | 4 / 4 | 6 / 6 | 5 / 5 | 17 / 17 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 2 / 2 | 2 / 10 | 8 / 18 | 1 / 13 | 1 / 7 | 1 / 6 | 1 / 4 | 2 / 6 | 3 / 5 | 4 / 17 |
Outcome results
Primary
Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D)
Certain toxicities will be considered dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease.
Time frame: After the first dose of treatment for up to 21 days.
Population: DLT-Evaluable
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 25 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 0 participants |
| 50 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 0 participants |
| 100 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 0 participants |
| 200 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 0 participants |
| 400 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 0 participants |
| 800 mg QD Fasted | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 0 participants |
| 800 mg QD Not Fasted | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 1 participants |
| 1000 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 2 participants |
| 1200 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 2 participants |
| 400 mg BID | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 0 participants |
| 600 mg BID | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 3 participants |
| 800 mg BID | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 3 participants |
| Safety Expansion Set 800 mg QD | Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D) | 1 participants |
Secondary
Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189
Adverse events will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) until 30 days post last dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 25 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 0 Participants |
| 50 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 0 Participants |
| 100 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 0 Participants |
| 200 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 2 Participants |
| 400 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 10 Participants |
| 800 mg QD Fasted | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 18 Participants |
| 800 mg QD Not Fasted | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 13 Participants |
| 1000 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 7 Participants |
| 1200 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 6 Participants |
| 400 mg BID | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 4 Participants |
| 600 mg BID | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 6 Participants |
| 800 mg BID | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 5 Participants |
| Safety Expansion Set 800 mg QD | Phase 1: Incidence of Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of BDTX-189 | 17 Participants |
Secondary
Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity
Objective response is defined as the proportion of participants who achieved a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.
Time frame: Assessed until disease progression or death for up to 12 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 25 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 25 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 0 Participants |
| 25 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 25 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 1 Participants |
| 25 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 25 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 0 Participants |
| 50 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 50 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 0 Participants |
| 50 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 0 Participants |
| 50 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 50 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 50 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 1 Participants |
| 100 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 100 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 100 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 0 Participants |
| 100 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 0 Participants |
| 100 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 100 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 1 Participants |
| 200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 2 Participants |
| 200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 0 Participants |
| 200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 0 Participants |
| 200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 400 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 4 Participants |
| 400 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 400 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 6 Participants |
| 400 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 0 Participants |
| 400 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 400 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 800 mg QD Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 800 mg QD Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 2 Participants |
| 800 mg QD Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 9 Participants |
| 800 mg QD Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 3 Participants |
| 800 mg QD Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 800 mg QD Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 4 Participants |
| 800 mg QD Not Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 1 Participants |
| 800 mg QD Not Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 3 Participants |
| 800 mg QD Not Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 2 Participants |
| 800 mg QD Not Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 1 Participants |
| 800 mg QD Not Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 5 Participants |
| 800 mg QD Not Fasted | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 1 Participants |
| 1000 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 0 Participants |
| 1000 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 3 Participants |
| 1000 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 1 Participants |
| 1000 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 1000 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 1000 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 3 Participants |
| 1200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 1 Participants |
| 1200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 2 Participants |
| 1200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 1 Participants |
| 1200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 1200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 2 Participants |
| 1200 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 400 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 400 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 1 Participants |
| 400 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 2 Participants |
| 400 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 1 Participants |
| 400 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 400 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 600 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 4 Participants |
| 600 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 600 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 600 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 0 Participants |
| 600 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 2 Participants |
| 600 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 800 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 1 Participants |
| 800 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| 800 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 1 Participants |
| 800 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| 800 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| 800 mg BID | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 3 Participants |
| Safety Expansion Set 800 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Non-complete response/non-partial response (non-CR/non-PR) | 0 Participants |
| Safety Expansion Set 800 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Partial response (PR) | 0 Participants |
| Safety Expansion Set 800 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Complete response (CR) | 0 Participants |
| Safety Expansion Set 800 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Progressive disease (PD) | 8 Participants |
| Safety Expansion Set 800 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Not evaluable (NE) | 2 Participants |
| Safety Expansion Set 800 mg QD | Phase 1: Objective Response Rate as a Preliminary Measure of Antitumor Activity | Stable disease (SD) | 7 Participants |
Secondary
Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics
Blood samples will be taken to measure the plasma concentrations of BDTX-189 in both a fed and fasted state.
Time frame: Multiple time points during Cycles 1-4 (each cycle is 21 days)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | NA Nanogram per mililiter (ng/mL) | — |
| 50 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | NA Nanogram per mililiter (ng/mL) | — |
| 100 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | NA Nanogram per mililiter (ng/mL) | — |
| 200 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 151 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 67.5 |
| 400 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 170 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 104 |
| 800 mg QD Fasted | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 268 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 72.7 |
| 800 mg QD Not Fasted | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 341 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 46.4 |
| 1000 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 0 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 0 |
| 1200 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 352 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 77.8 |
| 400 mg BID | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 123 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 133 |
| 600 mg BID | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 84.5 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 39 |
| 800 mg BID | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 165 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 53.8 |
| Safety Expansion Set 800 mg QD | Phase 1: Plasma Concentration of BDTX-189 as a Measure of Pharmacokinetics | 248 Nanogram per mililiter (ng/mL) | Geometric Coefficient of Variation 77.8 |
Secondary
Phase 1: Progression-free Survival as a Measure of Antitumor Activity
Progression-free survival is the time from first study dose until disease progression (PD; target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions) per RECIST v1.1.
Time frame: Assessed until disease progression or death for up to 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 25 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 0 Months |
| 50 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 0 Months |
| 100 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 0 Months |
| 200 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 1.61 Months |
| 400 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 1.866 Months |
| 800 mg QD Fasted | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 2.306 Months |
| 800 mg QD Not Fasted | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 5.158 Months |
| 1000 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 1.416 Months |
| 1200 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 1.572 Months |
| 400 mg BID | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 1.508 Months |
| 600 mg BID | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 2.252 Months |
| 800 mg BID | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 1.354 Months |
| Safety Expansion Set 800 mg QD | Phase 1: Progression-free Survival as a Measure of Antitumor Activity | 1.772 Months |