A Phase I/II, Dose Escalation and Expansion Study of TRI-611, an Oral ALK Molecular Glue Degrader in Participants With Advanced ALK-Positive NSCLC
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Study 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
To evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of TRI-611 in patients with ALK+ NSCLC.
The Phase 2 portion will further evaluate and characterize the efficacy and safety of TRI-611 across different patient cohorts
Main objective
1. To characterize the safety and tolerability of TRI-611 monotherapy to support the determination of the dose/regimen for further exploration or the recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD)
2. To evaluate the antitumor activity of TRI-611 monotherapy using RECIST v1.1
To evaluate TRI-611 (an oral ALK molecular gel degrader) in patients with advanced ALK-positive NSCLC
- * 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
- The Phase 1 portion enrolling ALK+ NSCLC patients, who have been previously treated with standard of care ALK tyrosine kinase therapies.
- 1 The Age be at least 18 years old when signing the informed consent form.
- 2 Pathologically confirmed ALK-positive non-small cell lung cancer (NSCLC)
- 3 An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- 4 Previously received anticancer treatment that met the requirements of the clinical trial protocol.
- 5 According to RECIST v1.1 criteria, measurable lesions are present.
- 6 Blood, kidneys, and liver function are good.
- 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 1 The tumor contains any other driver gene alterations that are known to induce resistance to ALK TKIs.
- 2 NSCLC contains histological components that have transformed into small cell lung cancer.
- 3 CNS metastases or spinal cord compression are present, accompanied by progressive neurological symptoms, or require increased Glucocorticoid dosage to control CNS disease.
- 4 The participants were not receiving any other cancer treatments or experimental drugs.
- 5 The participant was taking any of the drugs on the prohibited list unless a different drug could be used before the first dose.
- 6 A history of drug-induced interstitial lung disease, or any evidence of clinically active interstitial lung disease requiring steroid treatment.
- 7 The patient had undergone major surgery within 28 days prior to the first IMP administration.
- 8 Known allergy to TRI-611 or any of its components.
Clinical Study Information for Healthcare Providers
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