Advanced Nonhaematologic Malignancies
Conditions
Keywords
BOS172738, RET gene, Medullary Thyroid Cancer, Non-Small Cell Lung Cancer
Brief summary
This study will be conducted to assess the safety and tolerability of BOS172738 when administered to patients with advanced solid tumors with rearranged during transfection (RET) gene alterations and also to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of BOS172738.
Interventions
DRUGBOS172738
Oral capsules
Sponsors
Boston Pharmaceuticals
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
Participants are eligible to be included in the study only if all of the following criteria apply: * Male or female participants must be ≥ 18 years, at the time of signing the informed consent * Diagnosis of advanced solid tumor with a documented rearranged during transfection (RET) gene altered malignancy as determined locally by a DNA based assay of tumor tissue and/or blood * Participants must have no alternative approved therapy. * For participants in Part B expansion cohort only: documented local diagnosis of either 1) advanced RET gene fusion non-small cell lung cancer (NSCLC); 2) advanced RET gene mutant medullary thyroid cancer (MTC); or 3) other RET gene altered advanced tumors or NSCLC/MTC with prior specific RET gene targeted therapy * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Negative pregnancy test for females of child bearing potential; must be surgically sterile, postmenopausal, or willing and able to be compliant with a contraceptive regimen * Contraceptive use by men or women should be consistent with local regulations. * Capable of giving signed informed consent
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * Inability to take oral medications or gastrointestinal (GI) conditions that can interfere with the swallowing or absorption of study medication * Uncontrolled or severe concurrent medical condition * History of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug * Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug * Participants with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (testing not required) * Participants who are hepatitis B surface antigen positive or participants who are hepatitis C antibody positive (Participants who have been successfully treated for hepatitis C virus \[HCV\] are eligible if an undetectable HCV viral load at least 6 months after completion of treatment can be demonstrated.) * Any evidence of serious active infections * Uncontrolled or severe cardiovascular disease * Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements * Participants with a prior or concurrent malignancy other than the malignancies under study * Ongoing cancer directed therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with any treatment-emergent (TE) serious adverse event (SAE) | a minimum of approximately 3 months |
| Number of participants with any non-serious TEAE | a minimum of approximately 3 months |
| Number of participants with grade 3, grade 4, or grade 5 TEAEs | a minimum of approximately 3 months |
| Number of participants with any related TEAE | a minimum of approximately 3 months |
| Number of participants with any TEAE leading to study drug discontinuation | a minimum of approximately 3 months |
| Maximum tolerated dose (MTD) of BOS172738 | throughout Cycle 1 (each cycle is 28 days) |
| Recommended phase 2 dose (RP2D) of BOS172738 | 28-day cycles in Part A (minimum of one dose of BOS172738 received) |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) | a minimum of approximately 3 months |
| Part B: Plasma concentration of BOS172738 | Pre-dose on Day 1 of Cycles 2, 3, and 4 (each cycle is 28 days) |
| Objective Disease Control Rate (ODCR) | a minimum of approximately 3 months |
| Progression-Free Survival (PFS) | a minimum of approximately 3 months |
| Duration of Response (DoR) | a minimum of approximately 3 months |
| Time to Response (TTR) | a minimum of approximately 3 months |
| Duration of Complete Response (DoCR) | a minimum of approximately 3 months |
| Part A: Plasma concentration of BOS172738 | Pre-dose on Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, and 4. 15 minutes (min); 30 min; 1, 3, 6, 8, 10, and 12 hours after the BOS1722722 dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days) |
Countries
Belgium, France, Hong Kong, South Korea, Spain, Taiwan, United States
Outcome results
None listed