RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

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

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

Study Overview

• Status: Completed
• Conditions: Solid Tumor, Unspecified, Adult
• Intervention / Treatment: Drug: RLY-1971

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 Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Florida Cancer Specialist-Lake Mary
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists - Sarasota
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology; Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.; Other Names: GDC-1971; RO7517834

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in phospho-ERK levels	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	At the beginning of Cycle 1 Day 1 post and predose (Cycle = 21 days)
Tumor mutations by sequencing circulating tumor DNA (ctDNA)	Blood will be collected at screening and at End of Treatment on all patients	At the beginning of Cycle 1 Day 1
Duration of Response (DOR)	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	Through study completion (an average of one year)
Progression-free Survival (PFS)	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	Through study completion (an average of one year)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Actual): November 22, 2022
• Study Completion (Actual): November 22, 2022

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): December 19, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Phase 1; Solid Tumors; Advanced or Metastatic Solid Tumors; First in Human (FIH); SHP2 inhibition; PTPN11; Bypass Resistance; GDC-1971; RO7517834
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GO43242; REFMAL 678 (Other Identifier: Sarah Cannon Development Innovations)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No