ALK-Positive Lung Cancer, ALK-positive Non-small Cell Lung Cancer, ALK-positive NSCLC
Conditions
Brief summary
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
DRUGTRI-611
oral ALK molecular glue degrader
Sponsors
TRIANA Biomedicines, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 of the study consists of approximately 5 dose escalation cohorts and 2 backfill cohorts. Part 2 of the study consists of 3 cohorts of participants differentiated based on their previous treatment with ALK TKIs.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[in US only: '2 or more ALK TKIs'\], 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Treatment emergent adverse events | Within 28 days of the first TRI-611 dose | Treatment emergent adverse events (TEAEs) |
| Part 2: Objective response rate (ORR) | Approximately 16 weeks after the last participant dosed in Part 2 | Determine the objective response rate (ORR) based on RECIST v1.1 |
| Part 2: Depth of response (DofR) | Approximately 16 weeks after the last participant dosed in Part 2 | Defined as the greatest percentage reduction in the sum of diameters of target lesions from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Half-life (t1/2) of TRI-611 | Pre-dose and up to 24 hours post-dose | Determine the t1/2 of TRI-611 |
| Part 1: Area under the curve (AUC) of TRI-611 | Pre-dose and up to 24 hours post-dose | Determine the AUC of TRI-611 |
| Part 1: Maximum plasma concentration (Cmax) of TRI-611 | Pre-dose and up to 24 hours post-dose | Determine the Cmax of TRI-611 |
| Part 1: Minimum plasma concentration (Cmin) of TRI-611 | Pre-dose and up to 24 hours post-dose | Determine the Cmin of TRI-611 |
| Part 1: ORR | Approximately 16 weeks after the last participant dosed in Part 1 | Determine the ORR based on RECIST v1.1 |
| Part 1: DofR | Approximately 16 weeks after the last participant dosed in Part 1 | Defined as the greatest percentage reduction in the sum of diameters of target lesions from baseline |
| Parts 1&2: Duration of response (DOR) | Approximately 5 years after the last participant is dosed with TRI-611 | Determine the DOR based on RECIST v1.1 |
| Parts 1&2: Disease control rate (DCR) | Approximately 16 weeks after the last participant dosed | Defined as the number and percentage of participants who have achieved a response or stable disease based on RECIST v1.1 |
| Parts 1&2: Clinical Benefit Rate (CBR) | Approximately 9 months after the last participant is dosed | 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 |
| Parts 1&2: Progression-free survival (PFS) | Approximately 5 years after the last participant is dosed with TRI-611 | Determine PFS based on RECIST v1.1 |
| Parts 1&2: Overall survival (OS) | Approximately 5 years after the last participant is dosed with TRI-611 | Determine OS based on RECIST v1.1 |
| Parts 1&2: Central Nervous System (CNS) objective response rate (ORR) | Approximately 16 weeks after the last participant dosed | Determine CNS ORR based on modified RECIST (mRECIST v1.1) in participants with CNS metastasis at baseline |
| Parts 1&2: CNS duration of response (DOR) | Approximately 5 years after the last participant is dosed with TRI-611 | Determine CNS DOR based on mRECIST v1.1 in participants with CNS metastasis at baseline |
| Parts 1&2: Time to intracranial progression (TTP) | Approximately 5 years after the last participant is dosed with TRI-611 | Defined as the time to the date of the first documentation of objective progression of intracranial disease |
| Part 1: Profile changes in tumor ALK-fusion protein levels | Approximately 14 days after the last dose of participants in Part 1 that have consented to on-treatment biopsies | Assessing treatment-induced modulation of ALK expression only in participants consenting to on-treatment biopsies |
Countries
Australia, United States
Contacts
CONTACTTRIANA Clinical Trials
Outcome results
None listed