RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

NCT04252339 | Completed Phase 1 FDA Drug

• 2 other identifiers: GO43242REFMAL 678
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 6

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.

Conditions

Solid Tumor, Unspecified, Adult

Keywords

Solid Tumors; Advanced or Metastatic Solid Tumors; Phase 1; First in Human (FIH); SHP2 inhibition; PTPN11; Bypass Resistance; GDC-1971; RO7517834

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Plasma concentration levels of RLY-1971

  At the beginning of Cycle 1 & Cycle 2 (Each Cycle is 21 days)

• Objective Response Rate (ORR)

  Through study completion (an average of one year)

• Disease Control Rate (DCR)

  Through study completion (an average of one year)

Other Outcomes (4)

• Changes in phospho-ERK levels

  At the beginning of Cycle 1 Day 1 post and predose (Cycle = 21 days)

• Tumor mutations by sequencing circulating tumor DNA (ctDNA)

  At the beginning of Cycle 1 Day 1

• Duration of Response (DOR)

  Through study completion (an average of one year)

Study Arms (1)

RLY-1971 - Dose Escalation/Expansion

EXPERIMENTAL

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

Interventions

RLY-1971 DRUG

RLY-1971 is an oral inhibitor of SHP2.

Also known as: GDC-1971, RO7517834

RLY-1971 - Dose Escalation/Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

Florida Cancer Specialist-Lake Mary

Lake Mary, Florida, 32746, United States

Location

Florida Cancer Specialists - Sarasota

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Tennessee Oncology; Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Noonan Syndrome

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: February 5, 2020
• Study Start: February 4, 2020
• Primary Completion: November 22, 2022
• Study Completion: November 22, 2022
• Last Updated: January 31, 2023

Record last verified: 2023-01

Locations

US (6)