A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies
Overview
- Phase
- Phase 1
- Intervention
- eFT226
- Conditions
- Solid Tumor, Adult
- Sponsor
- Effector Therapeutics
- Enrollment
- 30
- Locations
- 14
- Primary Endpoint
- Part 2: (Combination Cohorts) Determine MTD
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of Zotatifin (eFT226) in subjects with selected advanced solid tumor malignancies.
Detailed Description
Part 1 (Dose Escalation): Completed; Recommended Phase 2 Dose (RP2D) and Maximum Tolerated Dose (MTD) identified Part 1a (Dose Escalation) This cohort will enroll patients with an advanced breast cancer that is refractory or intolerant to SOC therapy. Part 1b (Dose Escalation) This cohort will enroll patients with an advanced breast cancer that is refractory or intolerant to SOC therapy. Part 2 (Expansion Cohort) provides defined expansion cohorts to further explore the safety, pharmacology, and clinical activity of eFT226 monotherapy and in various combinations in subjects with previously treated advanced solid tumor malignancies.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part 1: Sequential escalation (Completed)
eFT226 administered IV weekly in 21-day cycles; dose escalated in sequential cohorts after subjects enrolled in a given cohort have completed DLT evaluation period.
Intervention: eFT226
Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS)
Cohort ECNS; Combination therapy partner administered per SOC at the approved dose.
Intervention: Sotorasib
Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK)
Cohort EMNK
Intervention: eFT226
Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF)
Cohort EMBF
Intervention: eFT226
Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH)
Cohort EMBH
Intervention: eFT226
Part 1b Dose Escalation, Combination, Breast
eFT226 administered IV every other week in 14-day cycles. Fulvestrant will also be given. Dose escalations per protocol.
Intervention: Fulvestrant
Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF)
Cohort ECBF; Combination therapy partner administered per SOC at the approved dose.
Intervention: Fulvestrant
Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1
ECBF-D1; Combination therapy partner administered per SOC at the approved dose.
Intervention: Fulvestrant
Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)
Cohort ECBF+A; Combination therapy partner administered per SOC at the approved dose.
Intervention: Fulvestrant
Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)
Cohort ECBF+A; Combination therapy partner administered per SOC at the approved dose.
Intervention: Abemaciclib
Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT)
Cohort ECBT; Combination therapy partner administered per SOC at the approved dose.
Intervention: Trastuzumab
Part 1a: Dose Escalation, Combination, Breast
eFT226 administered IV weekly in 21-day cycles. Fulvestrant will also be given. Dose escalations per protocol.
Intervention: Fulvestrant
Outcomes
Primary Outcomes
Part 2: (Combination Cohorts) Determine MTD
Time Frame: Through study completion, approximately 12 months
determined by occurrence of first cycle Dose Limiting Toxicities (DLTs) within the study design
Part 2: Percent change in tumor dimensions of target lesions- Efficacy
Time Frame: Through study completion, approximately 12 months
calculated by the percentage change from baseline in the sum of the LD of target lesions
Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs
Time Frame: Through study completion, approximately 12 months
according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Parts 1a and 1b: MTD
Time Frame: Through study completion, approximately 12 months
determined by occurrence of first cycle DLTs within a 3+3 or 3+3+3 clinical trial design
Parts 1a and 1b: RP2D
Time Frame: Through study completion, approximately 12 months
determine by Incidence, type, and severity of AEs and SAEs graded as per NCI CTCAE
Part 2: Objective Response Rate- Efficacy
Time Frame: Through study completion, approximately 12 months
defined as confirmed Complete Response (CR) or Partial Response (PR)
Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs
Time Frame: Through study completion, approximately 12 months
via adverse event monitoring
Part 2: (Combination Cohorts) Determine RP2D
Time Frame: Through study completion, approximately 12 months
determined by incidence and type of DLTs, and incidence, type, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Part 2: Time to Response (TTR)- Efficacy
Time Frame: Through study completion, approximately 12 months
defined as the interval from the start of study therapy to the first documentation of an objective response
Part 2: Duration of Response (DOR)- Efficacy
Time Frame: Through study completion, approximately 12 months
defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression or death from any cause
Secondary Outcomes
- Parts 1a and 1b: Objective response(Through study completion, approximately 12 months)
- Part 2: (Monotherapy and Combination Cohorts) Incidence and severity of AEs, SAEs, and additional safety parameters(Through study completion, approximately 12 months)
- Parts 1a and 1b: Percent change in tumor dimensions of target lesions(Through study completion, approximately 12 months)
- Parts 1a and 1b: DOR(Through study completion, approximately 12 months)
- Parts 1a and 1b: PFS(Through study completion, approximately 12 months)
- Evaluate plasma Pharmacokinetic (PK) parameters of eFT226including terminal state volume of distribution(Through study completion, approximately 12 months)
- Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant(Through study completion, approximately 12 months)
- Parts 1a and 1b: TTR(Through study completion, approximately 12 months)
- Evaluate plasma Pharmacokinetic (PK) parameters of eFT226(Through study completion, approximately 12 months)
- Part 2: Progression Free Survival(Through study completion, approximately 12 months)