RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT04252339
• Recruitment Status: Recruiting
• First Posted: February 5, 2020
• Last Update Posted: July 14, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Solid Tumor, Unspecified, Adult	Drug: RLY-1971	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 27, 2020
• Estimated Primary Completion Date: April 30, 2022
• Estimated Study Completion Date: April 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: RLY-1971 - Dose Escalation/Expansion; 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; RLY-1971 is an oral inhibitor of SHP2.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Plasma concentration levels of RLY-1971 [ Time Frame: At the beginning of Cycle 1 & Cycle 2 (Each Cycle is 21 days) ]
   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
2. Objective Response Rate (ORR) [ Time Frame: Through study completion (an average of one year) ]
   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
3. Disease Control Rate (DCR) [ Time Frame: Through study completion (an average of one year) ]
   DCR is defined as the percentage of response evaluable subjects who achieve a BOR of CR, PR or SD for at least 3 months

Other Outcome Measures:

1. Changes in phospho-ERK levels [ Time Frame: At the beginning of Cycle 1 Day 1 post and pre ]
   Blood will be collected at pre-dose at baseline on Cycle 1, Day 1 (C1D1) and at 3 time points (pre-dose, 2 hours post-dose, and 4 hours post-dose) on Cycle 1, Day 15 (C1D15) to assess the extent of target engagement
2. Tumor mutations by sequencing circulating tumor DNA (ctDNA) [ Time Frame: At the beginning of Cycle 1 Day 1 ]
   Blood will be collected at screening and at End of Treatment on all patients
3. Duration of Response (DOR) [ Time Frame: Through study completion (an average of one year) ]
   DOR is defined as the time from the participant's initial objective response (CR or PR) to RLY-1971, to disease progression or death due to any cause, whichever occurs first
4. Progression-free Survival (PFS) [ Time Frame: Through study completion (an average of one year) ]
   PFS is defined as the time from the start of study treatment to the first documented disease progression per RECIST v1.1, or death due to any cause, whichever occurs first

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subject is willing and able to provide written informed consent for the study prior to the performance of any study-specific procedures
2. Subject is a male or female subject ≥18 years of age at the time of consent
3. Subject must have an ECOG PS ≤ 1
4. Subject must have histologically or cytologically confirmed advanced or metastatic solid tumor
5. 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
6. Subject must have radiographically measurable or evaluable disease
7. Subject must have recovered from the reversible effects of prior anti-neoplastic therapy, except for alopecia and ≤ grade 2 neuropathy.
8. Subject has adequate end organ function
9. Subject is willing to comply with all protocol-required visits, assessments, and procedures
10. 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:

1. Subjects with documented history of tumor mutations that may not be amenable to treatment with RLY-1971, including:

   1. KRAS mutations: G12D, G12V, G13X, and Q61X
   2. BRAF V600E mutation
   3. MEK mutations
2. Subjects with prior antineoplastic therapy within 3 weeks of Study Day 1, or 5 half-lives, whichever is shorter
3. Subjects with prior palliative radiotherapy within 1 week of Study Day 1
4. Subjects who have had major surgery or trauma, or incomplete recovery from surgery or trauma, within 4 weeks of Study Day 1
5. 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.
6. Subjects with a history or evidence of ophthalmic disease
7. Subjects with a history or evidence of significant cardiac dysfunction
8. Subjects with a history or evidence of significant gastrointestinal disease
9. Subjects with other serious concurrent medical conditions
10. 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

Contacts and Locations

Contacts

Contact: Reference Study ID Number: GO43242 www.roche.com/about_roche/roche_worldwide.htm; 888-662-6728 (U.S.); global-roche-genentech-trials@gene.com

Locations

United States, Florida

Florida Cancer Specialists; Recruiting

Lake Mary, Florida, United States, 32746

Principal Investigator: Shekeab Jauhari, MD

Florida Cancer Specialists; Recruiting

Sarasota, Florida, United States, 34232

Principal Investigator: Judy Wang, MD

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator: Jessica Lin, MD

Dana Farber Cancer Center; Recruiting

Boston, Massachusetts, United States, 02115

Principal Investigator: Jessica Lin, MD

Sub-Investigator: Geoffrey Shapiro, MD

Beth Israel Deaconess Medical Center; Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator: Jessica Lin, MD

Sub-Investigator: Andrea Bullock, MD, MPH

United States, Tennessee

Tennessee Oncology; Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator: Joanna Bendell, MD

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04252339
• Other Study ID Numbers: GO43242; REFMAL 678 ( Other Identifier: Sarah Cannon Development Innovations )
• First Posted: February 5, 2020
• Last Update Posted: July 14, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hoffmann-La Roche:

Solid Tumors; Advanced or Metastatic Solid Tumors; Phase 1; First in Human (FIH); SHP2 inhibition; PTPN11; Bypass Resistance

Additional relevant MeSH terms:

Neoplasms