RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

Solid Tumor, Unspecified, Adult Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04252339
• Other study ID #: GO43242
• Secondary ID: REFMAL 678
• Status: Completed
• Phase: Phase 1
• Start date: February 4, 2020
• Est. completion date: November 22, 2022

Study information

• Verified date: January 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: November 22, 2022
• Est. primary completion date: November 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (ß-hCG) pregnancy test consistent with pregnancy obtained within 7 days before the first dose of study treatment

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Unspecified, Adult

Intervention

Drug:
• RLY-1971
RLY-1971 is an oral inhibitor of SHP2.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Florida Cancer Specialist-Lake Mary	Lake Mary	Florida
United States	Tennessee Oncology; Sarah Cannon Research Institute	Nashville	Tennessee
United States	Florida Cancer Specialists - Sarasota	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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
Other	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)
Other	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)
Primary	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
Primary	Recommended Phase 2 Dose (RP2D)	RP2D may be the same dose level or lower than the determined MTD.	Escalation Phase - 18 month Enrollment
Secondary	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)
Secondary	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)
Secondary	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)