Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04252339
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : February 23, 2021
Sponsor:
Information provided by (Responsible Party):
Relay Therapeutics, Inc.

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.

Layout table for study information
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 : July 1, 2021
Estimated Study Completion Date : April 30, 2022

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.




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04252339


Contacts
Layout table for location contacts
Contact: Relay Therapeutics, Inc. 617-322-0731 clinicaltrials@relaytx.com

Locations
Layout table for location information
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
Relay Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Chair: Joanna Bendell, MD SCRI-Tennessee Oncology
Layout table for additonal information
Responsible Party: Relay Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04252339    
Other Study ID Numbers: RLY-1971-101
REFMAL 678 ( Other Identifier: Sarah Cannon Development Innovations )
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: February 23, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Relay Therapeutics, Inc.:
Solid Tumors
Advanced or Metastatic Solid Tumors
Phase 1
First in Human (FIH)
SHP2 inhibition
PTPN11
Bypass Resistance
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms