A Phase 1/2 Study of TRI-611 in ALK-Positive NSCLC

Official title

A Phase 1/2, Dose Escalation and Expansion Study of TRI-611, an Oral ALK Molecular Glue Degrader in Participants With Advanced ALK-Positive NSCLC

Overview

The goal of this clinical trial is to learn about the safety and recommended dose of TRI-611 when administered to adults with ALK-positive non-small cell lung cancer (NSCLC). The trial will also evaluate the antitumor activity of TRI-611 in adults with ALK-positive NSCLC. The study will be conducted in two parts. The first part will examine different doses of TRI-611. The second part will look at how well TRI-611 works on ALK-positive NSCLC when administered to three groups of participants that differ based on what type of prior therapy they have received. In this study participants will: * Take TRI-611 on a continued basis, provided it is well-tolerated, for as long as their disease is not progressing * Visit the clinic approximately seven times in the first 3 months and then just once at the start of each 28-day cycle thereafter * Keep a diary of each time they take the study medication

Detailed description

This is a Phase 1/2 dose escalation and dose expansion study designed to evaluate the safety and tolerability of TRI-611, identify the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in participants with ALK-positive NSCLC.

Part 1 of the study consists of a dose escalation to determine the MTD and/or recommended dose(s) of TRI-611 for further exploration in two backfill cohorts.

Following completion of Part 1 of the study, Part 2 of the study will be initiated. The second part of the study is comprised of three cohorts (M1, M2, M3) of participants differentiated based on their previous treatment with ALK TKIs (tyrosine kinase inhibitors). During this part of the study the antitumor activity of TRI-611 will be further explored. See eligibility criteria for more details.

Interventions

• Drug TRI-611
  oral ALK molecular glue degrader

Primary outcome measures

• Part 1: Treatment emergent adverse events [Time frame: Within 28 days of the first TRI-611 dose]
• Part 2: Objective response rate (ORR) [Time frame: Approximately 16 weeks after the last participant dosed in Part 2]
• Part 2: Depth of response (DofR) [Time frame: Approximately 16 weeks after the last participant dosed in Part 2]

Secondary outcome measures (12)

• Part 1: Half-life (t1/2) of TRI-611 [Time frame: Pre-dose and up to 24 hours post-dose]
• Part 1: Area under the curve (AUC) of TRI-611 [Time frame: Pre-dose and up to 24 hours post-dose]
• Part 1: Maximum plasma concentration (Cmax) of TRI-611 [Time frame: Pre-dose and up to 24 hours post-dose]
• Part 1: Minimum plasma concentration (Cmin) of TRI-611 [Time frame: Pre-dose and up to 24 hours post-dose]
• Part 1: ORR [Time frame: Approximately 16 weeks after the last participant dosed in Part 1]
• Part 1: DofR [Time frame: Approximately 16 weeks after the last participant dosed in Part 1]
• Parts 1&2: Duration of response (DOR) [Time frame: Approximately 5 years after the last participant is dosed with TRI-611]
• Parts 1&2: Disease control rate (DCR) [Time frame: Approximately 16 weeks after the last participant dosed]
• Parts 1&2: Clinical Benefit Rate (CBR) [Time frame: Approximately 9 months after the last participant is dosed]
• Parts 1&2: Progression-free survival (PFS) [Time frame: Approximately 5 years after the last participant is dosed with TRI-611]
• Parts 1&2: Overall survival (OS) [Time frame: Approximately 5 years after the last participant is dosed with TRI-611]
• Parts 1&2: Central Nervous System (CNS) objective response rate (ORR) [Time frame: Approximately 16 weeks after the last participant dosed]

Eligibility criteria

Inclusion criteria

• Pathologically confirmed diagnosis of ALK-positive non-small cell lung cancer (NSCLC)
• Measurable disease per RECIST v1.1
• Adequate bone marrow reserve and organ function
• Part 1: prior treatment with 2 to 3 ALK TKIs, prior treatment with lorlatinib is required but must not have been in the first line
• Part 2 Cohort M1: prior treatment with 2 to 3 ALK TKIs, prior treatment with lorlatinib is required but must not have been in the first line, prior treatment with neladalkib is excluded
• Part 2 Cohort M2: prior treatment with more than 3 ALK TKIs, prior treatment with lorlatinib and neladalkib is required but neither may have been in the first line
• Part 2 Cohort M3: participants without prior ALK TKI treatment

Exclusion criteria

• Participant's cancer has any additional driver alterations known to be a mechanism of resistance to ALK TKIs
• For participants with central nervous system (CNS) metastases or spinal cord compression, they must not be associated with progressive neurological symptoms or require increasing doses of corticosteroids to control the CNS disease
• Ongoing treatment with another anticancer treatment or investigational agent
• Known allergy/hypersensitivity to TRI-611 or any of its ingredients
• Major surgery within 4 weeks of receiving the first dose of TRI-611

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• UCSF — San Francisco
• University of Colorado Cancer Center — Aurora
• Massachusetts General Hospital — Boston
• Dana Farber Cancer Center — Boston
• Washington University Medical Center — St Louis
• Memorial Sloan-Kettering Cancer Center — New York
• Duke University — Durham
• Taylor Cancer Research Center — Maumee
• … and 4 more centers

Identifiers

NCT: NCT07491497 · TRI-611-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗