Clinical trial NCT04252339: RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Escalation Phase - 18 month Enrollment
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Escalation Phase - 18 month Enrollment
Secondary outcomes:
measure: Plasma concentration levels of RLY-1971
timeFrame: At the beginning of Cycle 1 & Cycle 2 (Each Cycle is 21 days)
measure: Objective Response Rate (ORR)
timeFrame: Through study completion (an average of one year)
measure: Disease Control Rate (DCR)
timeFrame: Through study completion (an average of one year)
Other outcomes:
measure: Changes in phospho-ERK levels
timeFrame: At the beginning of Cycle 1 Day 1 post and predose (Cycle = 21 days)
measure: Tumor mutations by sequencing circulating tumor DNA (ctDNA)
timeFrame: At the beginning of Cycle 1 Day 1
measure: Duration of Response (DOR)
timeFrame: Through study completion (an average of one year)
measure: Progression-free Survival (PFS)
timeFrame: Through study completion (an average of one year)
Locations:
city: Lake Mary
country: United States
facility: Florida Cancer Specialist-Lake Mary
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Nashville
country: United States
facility: Tennessee Oncology; Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: