RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This study is a multi-center, open-label, dose escalation and expansion study of RLY-1971 in subjects with advanced or metastatic solid tumors.

Detailed Description
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Dose escalation/dose expansion study to assess the MTD, safety, tolerability, PK and preliminary anti-tumor activity of RLY-1971. Approximately 70 patients

Official Title
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Phase 1, Open Label, Dose Escalation and Expansion Study of RLY-1971, a Highly Potent and Selective SHP2 Inhibitor, in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumor, Unspecified, Adult

Intervention / Treatment
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* Drug: RLY-1971


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is willing and able to provide written informed consent for the study prior to the performance of any study-specific procedures Subject is a male or female subject ≥18 years of age at the time of consent Subject must have an ECOG PS ≤ 1 Subject must have histologically or cytologically confirmed advanced or metastatic solid tumor Subjects who are refractory to FDA-approved, standard therapy or for which standard or curative therapy does not exist or is not considered sufficient or appropriate by the patient or Investigator Subject must have radiographically measurable or evaluable disease Subject must have recovered from the reversible effects of prior anti-neoplastic therapy, except for alopecia and ≤ grade 2 neuropathy. Subject has adequate end organ function Subject is willing to comply with all protocol-required visits, assessments, and procedures Male and female subjects of child-bearing potential are willing to use medically acceptable methods of birth control from the screening visit through 30 days after the last dose of study medication Exclusion Criteria: Subjects with documented history of tumor mutations that may not be amenable to treatment with RLY-1971, including: KRAS mutations: G12D, G12V, G13X, and Q61X BRAF V600E mutation MEK mutations Subjects with prior antineoplastic therapy within 3 weeks of Study Day 1, or 5 half-lives, whichever is shorter Subjects with prior palliative radiotherapy within 1 week of Study Day 1 Subjects who have had major surgery or trauma, or incomplete recovery from surgery or trauma, within 4 weeks of Study Day 1 Subjects with known central nervous system (CNS) metastases or primary CNS tumor that is associated with progressive neurologic symptoms or requires increasing doses of corticosteroids to control the CNS disease. If patient requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks preceding C1D1, or subject has new lesions appearing on follow up brain MRI that require CNS-directed intervention. Subjects with a history or evidence of ophthalmic disease Subjects with a history or evidence of significant cardiac dysfunction Subjects with a history or evidence of significant gastrointestinal disease Subjects with other serious concurrent medical conditions Subject is pregnant, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy obtained within 7 days before the first dose of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RLY-1971 - Dose Escalation/Expansion<br>Dose Escalation: Oral dose of RLY-1971 until Maximum Tolerated Dose (MTD), and Recommended Phase 2 dose (RP2D) are identified Dose Expansion: Oral dose of RLY-1971 once Maximum Tolerated Dose (MTD), and Recommended Phase 2 Dose (RP2D) are identified. | Drug: RLY-1971<br>* RLY-1971 is an oral inhibitor of SHP2.<br>* Other names: RO7517834;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | MTD is defined as a dose level immediately below that at which ≥2 of 6 subjects experience a DLT during the first cycle. | Escalation Phase - 18 month Enrollment | 
| Recommended Phase 2 Dose (RP2D) | RP2D may be the same dose level or lower than the determined MTD. | Escalation Phase - 18 month Enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration levels of RLY-1971 | Blood samples may be taken at pre-dose, 0.5, 1, 2, 4, 6, and 8hrs on Cycle 1 Day 1 and 15, 24 hrs post dose on Cycle 1 Day 2, and pre-dose on Cycle 2 Day 1 | At the beginning of Cycle 1 & Cycle 2 (Each Cycle is 21 days) | 
| Objective Response Rate (ORR) | Evaluation by RECIST 1.1; ORR is defined as the proportion of subjects in the response evaluable population who achieve the best overall response (BOR) of CR or PR | Through study completion (an average of one year) | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of response evaluable subjects who achieve a BOR of CR, PR or SD for at least 3 months | Through study completion (an average of one year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHP2 inhibition, PTPN11, Bypass Resistance, GDC-1971, RO7517834, Solid Tumors, Advanced or Metastatic Solid Tumors, Phase 1, First in Human (FIH)