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

NCT03780517 | Completed Phase 1 FDA Drug

• 2 other identifiers: BOS172738-012018-002612-27
• Study Type: interventional
• Target: 117
• Locations: 7 countries
• Sites: 21

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.

Conditions

Advanced Nonhaematologic Malignancies

Keywords

BOS172738; RET gene; Medullary Thyroid Cancer; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (8)

• Objective Response Rate (ORR)

  a minimum of approximately 3 months

• 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

Study Arms (1)

BOS172738

EXPERIMENTAL

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.

Drug: BOS172738

Interventions

BOS172738 DRUG

Oral capsules

BOS172738

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Pharmaceuticals: lead

Study Sites (21)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Jules Bordet

Brussels, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Institut Bergonié

Bordeaux, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital Pitié-Salpêtrière

Paris, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Chungbuk National University Hospital

Cheongju-si, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University College of Medicine

Seoul, South Korea

Location

Hospital Universitario Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Spain

Location

Instituto Oncológico Dr. Rosell, S.L.

Barcelona, Spain

Location

Start Madrid - Ciocc

Madrid, Spain

Location

START MADRID-FJD, Hospital Fundación Jiménez Díaz

Madrid, Spain

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Multiple Endocrine Neoplasia Type 2a; Carcinoma, Medullary; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 19, 2018
• Study Start: December 12, 2018
• Primary Completion: September 26, 2023
• Study Completion: September 26, 2023
• Last Updated: October 30, 2023

Record last verified: 2023-10

Locations

HK (1); US (2); FR (4); BE (2); KR (5); ES (5); TW (2)