This study is a multi-center, open-label, dose escalation study of RLY-1971 in subjects with advanced or metastatic solid tumors.
Name: RLY-1971
Description: Blood samples may be taken at pre-dose, 0.5, 1, 2, 4, 6, and 8hrs on Cycle I Day 1 and 15, 24 hrs post dose on Cycle 1 Day 2, 48hrs post dose on Cycle 1 Day 3, and post dose on Cycle 2 Day 1
Measure: Plasma concentration levels of RLY-1971 Time: At the beginning of Cycle 1 & Cycle 2 (Each Cycle is 21 days)Description: 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
Measure: Objective Response Rate (ORR) Time: Through study completion (an average of one year)Description: DCR is defined as the percentage of response evaluable subjects who achieve a BOR of CR, PR or SD for at least 3 months
Measure: Disease Control Rate (DCR) Time: Through study completion (an average of one year)Description: 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.
Measure: Changes in phospho-ERK levels Time: At the beginning of Cycle 1 Day 1 post and preDescription: Blood will be collected at screening and at End of Treatment on all patients
Measure: Tumor mutations by sequencing circulating tumor DNA (ctDNA) Time: At the beginning of Cycle 1 Day 1Description: 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
Measure: Duration of Response (DOR) Time: Through study completion (an average of one year)Description: TTR is defined as the period of time from the date of first the dose of RLY-1971 administration until the first objective documentation of response.
Measure: Time to Response (TTR) Time: Through study completion (an average of one year)Description: TTP is defined as the interval between the first dose of RLY-1971 until disease progression
Measure: Time to Progression (TTP) Time: Through study completion (an average of one year)Description: 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
Measure: Progression-free Survival (PFS). Time: Through study completion (an average of one year)Sequential Assignment
There are 3 SNPs
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) primary tumor, uncontrolled CNS metastases, or carcinomatous meningitis. --- G12D ---
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) primary tumor, uncontrolled CNS metastases, or carcinomatous meningitis. --- G12D --- --- G12V ---
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) primary tumor, uncontrolled CNS metastases, or carcinomatous meningitis. --- G12D --- --- G12V --- --- V600E ---