Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies (Zotatifin)

Effector Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor, Adult

Treatments: Drug: Fulvestrant; Drug: Sotorasib; Drug: Abemaciclib; Drug: Trastuzumab; Drug: eFT226

Study type: Interventional

Funder types: Industry

Identifiers

NCT04092673

eFT226-0002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 11 patient groups

Part 1: Sequential escalation (Completed)

Experimental group

Description:

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.

Treatment:

Drug: eFT226

Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK)

Experimental group

Description:

Cohort EMNK

Treatment:

Drug: eFT226

Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF)

Experimental group

Description:

Cohort EMBF

Treatment:

Drug: eFT226

Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH)

Experimental group

Description:

Cohort EMBH

Treatment:

Drug: eFT226

Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF)

Experimental group

Description:

Cohort ECBF; Combination therapy partner administered per SOC at the approved dose.

Treatment:

Drug: Fulvestrant

Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS)

Experimental group

Description:

Cohort ECNS; Combination therapy partner administered per SOC at the approved dose.

Treatment:

Drug: Sotorasib

Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)

Experimental group

Description:

Cohort ECBF+A; Combination therapy partner administered per SOC at the approved dose.

Treatment:

Drug: Abemaciclib

Drug: Fulvestrant

Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT)

Experimental group

Description:

Cohort ECBT; Combination therapy partner administered per SOC at the approved dose.

Treatment:

Drug: Trastuzumab

Part 1a: Dose Escalation, Combination, Breast

Experimental group

Description:

eFT226 administered IV weekly in 21-day cycles. Fulvestrant will also be given. Dose escalations per protocol.

Treatment:

Drug: Fulvestrant

Part 1b Dose Escalation, Combination, Breast

Experimental group

Description:

eFT226 administered IV every other week in 14-day cycles. Fulvestrant will also be given. Dose escalations per protocol.

Treatment:

Drug: Fulvestrant

Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1

Experimental group

Description:

ECBF-D1; Combination therapy partner administered per SOC at the approved dose.

Treatment:

Drug: Fulvestrant