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

Phase 2RecruitingNCT07491497

TRIANA Biomedicines, Inc.160 enrolled

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

160

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (7)

University of Colorado Cancer Center

Aurora, Colorado, United States

RECRUITING

Washington University Medical Center

St Louis, Missouri, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

RECRUITING

START Mountain Region

West Valley City, Utah, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

RECRUITING

Outcomes

Primary Outcomes

Part 1: Treatment emergent adverse events

Treatment emergent adverse events (TEAEs)

Time frame: Within 28 days of the first TRI-611 dose

Part 2: Objective response rate (ORR)

Determine the objective response rate (ORR) based on RECIST v1.1

Time frame: Approximately 16 weeks after the last participant dosed in Part 2

Part 2: Depth of response (DofR)

Defined as the greatest percentage reduction in the sum of diameters of target lesions from baseline

Time frame: Approximately 16 weeks after the last participant dosed in Part 2

Secondary Outcomes

Part 1: Half-life (t1/2) of TRI-611

Determine the 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

Determine the AUC of TRI-611

Time frame: Pre-dose and up to 24 hours post-dose

Part 1: Maximum plasma concentration (Cmax) of TRI-611

Determine the Cmax of TRI-611

Time frame: Pre-dose and up to 24 hours post-dose

Part 1: Minimum plasma concentration (Cmin) of TRI-611

Determine the Cmin of TRI-611

Time frame: Pre-dose and up to 24 hours post-dose

Part 1: ORR

Determine the ORR based on RECIST v1.1

Time frame: Approximately 16 weeks after the last participant dosed in Part 1

Part 1: DofR

Defined as the greatest percentage reduction in the sum of diameters of target lesions from baseline

Time frame: Approximately 16 weeks after the last participant dosed in Part 1

Parts 1&2: Duration of response (DOR)

Determine the DOR based on RECIST v1.1

Time frame: Approximately 5 years after the last participant is dosed with TRI-611

Parts 1&2: Disease control rate (DCR)

Defined as the number and percentage of participants who have achieved a response or stable disease based on RECIST v1.1

Time frame: Approximately 16 weeks after the last participant dosed

Parts 1&2: Clinical Benefit Rate (CBR)

Defined as the number and percentage of participants who have achieved a response or stable disease based on RECIST v1.1 maintained for a minimum of 6 months

Time frame: Approximately 9 months after the last participant is dosed

Parts 1&2: Progression-free survival (PFS)

Determine PFS based on RECIST v1.1

Time frame: Approximately 5 years after the last participant is dosed with TRI-611

Parts 1&2: Overall survival (OS)

Determine OS based on RECIST v1.1

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)

Determine CNS ORR based on modified RECIST (mRECIST v1.1) in participants with CNS metastasis at baseline

Time frame: Approximately 16 weeks after the last participant dosed

Parts 1&2: CNS duration of response (DOR)

Determine CNS DOR based on mRECIST v1.1 in participants with CNS metastasis at baseline

Time frame: Approximately 5 years after the last participant is dosed with TRI-611

Parts 1&2: Time to intracranial progression (TTP)

Defined as the time to the date of the first documentation of objective progression of intracranial disease

Time frame: Approximately 5 years after the last participant is dosed with TRI-611

Part 1: Profile changes in tumor ALK-fusion protein levels

Assessing treatment-induced modulation of ALK expression only in participants consenting to on-treatment biopsies

Time frame: Approximately 14 days after the last dose of participants in Part 1 that have consented to on-treatment biopsies

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

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts