Clinical trial NCT04092673: Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies
Official title: A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Lead sponsor: Effector Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-09-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation, 3+3, 3+3+3
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Parts 1a and 1b: MTD
timeFrame: Through study completion, approximately 12 months
measure: Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs
timeFrame: Through study completion, approximately 12 months
measure: Parts 1a and 1b: RP2D
timeFrame: Through study completion, approximately 12 months
measure: Parts 1a and 1b: RP2D
timeFrame: Through study completion, approximately 12 months
measure: Part 2: Objective Response Rate- Efficacy
timeFrame: Through study completion, approximately 12 months
measure: Part 2: (Combination Cohorts) Determine MTD
timeFrame: Through study completion, approximately 12 months
measure: Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs
timeFrame: Through study completion, approximately 12 months
measure: Part 2: (Combination Cohorts) Determine RP2D
timeFrame: Through study completion, approximately 12 months
measure: Part 2: Percent change in tumor dimensions of target lesions- Efficacy
timeFrame: Through study completion, approximately 12 months
measure: Part 2: Time to Response (TTR)- Efficacy
timeFrame: Through study completion, approximately 12 months
measure: Part 2: Duration of Response (DOR)- Efficacy
timeFrame: Through study completion, approximately 12 months
Secondary outcomes:
measure: Parts 1a and 1b: Objective response
timeFrame: Through study completion, approximately 12 months
measure: Parts 1a and 1b: Percent change in tumor dimensions of target lesions
timeFrame: Through study completion, approximately 12 months
measure: Parts 1a and 1b: TTR
timeFrame: Through study completion, approximately 12 months
measure: Parts 1a and 1b: DOR
timeFrame: Through study completion, approximately 12 months
measure: Parts 1a and 1b: PFS
timeFrame: Through study completion, approximately 12 months
measure: Part 2: (Monotherapy and Combination Cohorts) Incidence and severity of AEs, SAEs, and additional safety parameters
timeFrame: Through study completion, approximately 12 months
measure: Part 2: Progression Free Survival
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226including terminal state volume of distribution
timeFrame: Through study completion, approximately 12 months
measure: Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant
timeFrame: Through study completion, approximately 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center- Monmouth
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center- Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center- Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center- David H. Koch Center for Cancer Care
state: New York
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: New Experimental Therapeutics of San Antonio - NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: EFFECTOR Therapeutics, Inc.
name: Douglas Warner, MD
role: STUDY_DIRECTOR
References: