Safety, Efficacy, and Tolerability of BOS172738 in Patients With Advanced Rearranged During Transfection (RET) Gene-Altered Tumors

Boston Scientific

Status and phase: Completed; Phase 1

Conditions: Advanced Nonhaematologic Malignancies

Treatments: Drug: BOS172738

Study type: Interventional

Funder types: Industry

Identifiers

NCT03780517

2018-002612-27 (EudraCT Number)

BOS172738-01

Details and patient eligibility

About

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.

Enrollment: 117 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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117 participants in 1 patient group

BOS172738

Experimental group

Description:

In Part A (dose escalation), participants with advanced solid tumors with rearranged during transfection (RET) gene alterations will receive oral BOS172738 at a starting dose of 10 milligrams (mg) once daily in each 28-day cycle. In Part B (dose expansion), participants with RET gene-fusion non-small cell lung cancer (NSCLC), with RET gene-mutant medullary thyroid cancer (MTC), and with RET gene-altered advanced tumors or NSCLC/MTC with prior specific RET gene-targeted therapy will be enrolled in Cohorts 1, 2, and 3, respectively, and will receive oral BOS172738 once daily in each 28-day cycle at the recommended Phase 2 dose (RP2D) established in Part A.

Treatment:

Drug: BOS172738