Solid Tumor, Adult Clinical Trial
— ZotatifinOfficial title:
A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies
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.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | March 31, 2025 |
Est. primary completion date | December 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Key Criteria: Parts 1a and 1b (Dose Escalation + Fulvestrant): - Patient has histological or cytological confirmation of breast cancer. - Patient has metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit. - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows: - Minimum of one prior line of therapy for advanced/metastatic disease. - Maximum of five prior lines of therapy for advanced/metastatic disease. - Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting. - Prior treatment has included a CDK4/6 inhibitor. - Tumor is ER+ (defined as ER IHC staining > 0%). Cohort EMNK: - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1 agent, if appropriate. - Tumor has a known KRAS-activating mutation; Patients with KRAS G12C mutations are excluded. Cohort EMBF: - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows: - Minimum of one prior line of therapy for advanced/metastatic disease. - Maximum of five prior lines of therapy for advanced/metastatic disease. - Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting, which may include combination therapy (eg, with a CDK4/6 inhibitor). - Tumor is ER+ (defined as ER IHC staining > 0%) and has FGFR amplification. Cohort EMBH: - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows: - Minimum of one prior line of therapy for advanced/metastatic disease. - Minimum of one line of HER2-directed therapy Note: Prior treatment with CDK4/6 inhibitors is permitted. - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+). Cohort ECNS: - Patient has histologically or cytologically confirmed stage IIIB (pleural or pericardial effusion) or stage IV NSCLC. - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1 agent, if appropriate. Note: Patients who have declined approved therapy(ies) or who per treating physician are not eligible for approved therapy(ies) (eg, due to intolerance) may be eligible following discussion with the Medical Monitor. - Tumor has a known G12C KRAS-activating mutation. Note: Patients who have been previously treated with KRAS-specific therapy are excluded. Cohort ECBF: - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows: - Minimum of one prior line of therapy for advanced/metastatic disease. - Maximum of five prior lines of therapy for advanced/metastatic disease. - Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting. - Prior treatment has included a CDK4/6 inhibitor. - Tumor is ER+ (defined as ER IHC staining > 0%). Cohort ECBF+A: - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows: - Minimum of one prior line of therapy for advanced/metastatic disease. - Maximum of five prior lines of therapy for advanced/metastatic disease. - Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting. - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2- (defined as absence of HER2 3+ IHC staining and/or absence of FISH+). Cohort ECBT: - Patient has progressed after treatment with at least one approved anti-HER2 agent and has been administered at least one line of chemotherapy. - Tumor is HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+). Cohorts EMBF, EMBH, ECBF, ECBF+A: There is no limit on the number of lines of prior endocrine therapies. Cohort ECBF-D1: - Patient has metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit. - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows: - Minimum of one prior line of therapy for advanced/metastatic disease. - Maximum of five prior lines of therapy for advanced/metastatic disease. - Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting. - Prior treatment has included a CDK4/6 inhibitor. - Tumor is ER+ (defined as ER IHC staining > 0%). - Tumor has amplification of Cyclin D1 as determined by next generation sequencing or in situ hybridization. |
Country | Name | City | State |
---|---|---|---|
United States | Memorial Sloan Kettering Cancer Center- Commack | Commack | New York |
United States | Virginia Cancer Specialists | Fairfax | Virginia |
United States | START Midwest | Grand Rapids | Michigan |
United States | Memorial Sloan Kettering Cancer Center- Westchester | Harrison | New York |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada |
United States | University of Southern California | Los Angeles | California |
United States | Valkyrie Clinical Trials | Los Angeles | California |
United States | Memorial Sloan Kettering Cancer Center- Monmouth | Middletown | New Jersey |
United States | Memorial Sloan Kettering Cancer Center- David H. Koch Center for Cancer Care | New York | New York |
United States | Hoag Memorial Hospital Presbyterian | Newport Beach | California |
United States | Stanford University | Palo Alto | California |
United States | New Experimental Therapeutics of San Antonio - NEXT Oncology | San Antonio | Texas |
United States | University of Toledo Medical Center | Toledo | Ohio |
Lead Sponsor | Collaborator |
---|---|
Effector Therapeutics |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Parts 1a and 1b: MTD | determined by occurrence of first cycle DLTs within a 3+3 or 3+3+3 clinical trial design | Through study completion, approximately 12 months | |
Primary | Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs | according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) | Through study completion, approximately 12 months | |
Primary | Parts 1a and 1b: RP2D | determined by Incidence and type of DLTs | Through study completion, approximately 12 months | |
Primary | Parts 1a and 1b: RP2D | determine by Incidence, type, and severity of AEs and SAEs graded as per NCI CTCAE | Through study completion, approximately 12 months | |
Primary | Part 2: Objective Response Rate- Efficacy | defined as confirmed Complete Response (CR) or Partial Response (PR) | Through study completion, approximately 12 months | |
Primary | Part 2: (Combination Cohorts) Determine MTD | determined by occurrence of first cycle Dose Limiting Toxicities (DLTs) within the study design | Through study completion, approximately 12 months | |
Primary | Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs | via adverse event monitoring | Through study completion, approximately 12 months | |
Primary | Part 2: (Combination Cohorts) Determine RP2D | determined by incidence and type of DLTs, and incidence, type, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Through study completion, approximately 12 months | |
Primary | Part 2: Percent change in tumor dimensions of target lesions- Efficacy | calculated by the percentage change from baseline in the sum of the LD of target lesions | Through study completion, approximately 12 months | |
Primary | Part 2: Time to Response (TTR)- Efficacy | defined as the interval from the start of study therapy to the first documentation of an objective response | Through study completion, approximately 12 months | |
Primary | Part 2: Duration of Response (DOR)- Efficacy | 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 | Through study completion, approximately 12 months | |
Secondary | Parts 1a and 1b: Objective response | determined by confirmed CR or PR | Through study completion, approximately 12 months | |
Secondary | Parts 1a and 1b: Percent change in tumor dimensions of target lesions | calculated by the percentage change from baseline in the sum of the LD of target lesions | Through study completion, approximately 12 months | |
Secondary | Parts 1a and 1b: TTR | defined as the interval from the start of study therapy to the first documentation of an objective response | Through study completion, approximately 12 months | |
Secondary | Parts 1a and 1b: DOR | 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 | Through study completion, approximately 12 months | |
Secondary | Parts 1a and 1b: PFS | defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause | Through study completion, approximately 12 months | |
Secondary | Part 2: (Monotherapy and Combination Cohorts) Incidence and severity of AEs, SAEs, and additional safety parameters | via adverse event monitoring | Through study completion, approximately 12 months | |
Secondary | Part 2: Progression Free Survival | defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 | including area under the plasma concentration-time curve | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 | including maximum concentration | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 | including terminal phase rate constant | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 | including estimated steady-state volume of distribution [Vss] | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 | including half-life (t½) | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 | including total body clearance | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226including terminal state volume of distribution | including terminal state volume of distribution | Through study completion, approximately 12 months | |
Secondary | Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant | including terminal phase rate constant | Through study completion, approximately 12 months |
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