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

A Phase 1 Study of BOS172738 in Patients With Advanced Solid Tumors With RET Gene Alterations Including Non-Small Cell Lung Cancer (NSCLC) and Medullary Thyroid Cancer (MTC)

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.

Study Overview

• Status: Completed
• Conditions: Advanced Nonhaematologic Malignancies
• Intervention / Treatment: Drug: BOS172738

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Institut Jules Bordet
  • Leuven, Belgium
    • UZ Leuven
• France
  • Bordeaux, France
    • Institut Bergonie
  • Lyon, France
    • Centre Leon Berard
  • Paris, France
    • Hôpital Pitié-Salpêtrière
  • Villejuif, France
    • Institut Gustave Roussy
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• Korea, Republic of
  • Cheongju-si, Korea, Republic of
    • Chungbuk National University Hospital
  • Gyeonggi-do, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University College of Medicine
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
• Spain
  • Badalona, Spain
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain
    • Instituto Oncológico Dr. Rosell, S.L.
  • Madrid, Spain
    • START Madrid-FJD, Hospital Fundación Jiménez Díaz
  • Madrid, Spain
    • START Madrid - CIOCC
  • Andalucia
    • Málaga, Andalucia, Spain, 29010
      • Hospital Universitario Virgen de La Victoria
• Taiwan
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BOS172738; 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; Oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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
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)
Part B: Plasma concentration of BOS172738	Pre-dose on Day 1 of Cycles 2, 3, and 4 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Boston Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): September 26, 2023
• Study Completion (Actual): September 26, 2023

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Medullary Thyroid Cancer; BOS172738; RET gene
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BOS172738-01; 2018-002612-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes