What side effects are associated with this type of intervention?

Treatments for solid tumors that inhibit protein synthesis, such as Zotatifin (eFT226), commonly cause gastrointestinal issues (nausea, vomiting, diarrhea), hematologic toxicities (anemia, neutropenia), fatigue, and liver enzyme abnormalities. Specific agents may also have unique side effects, such as renal impairment or skin reactions.

What prior FDA approvals exist?

FDA-approved treatments for solid tumors often target various pathways involved in tumor growth and proliferation. While specific inhibitors of eIF4A like Zotatifin (eFT226) are still under investigation, other approved drugs target related mechanisms. For example, mTOR inhibitors like temsirolimus and everolimus disrupt protein synthesis and cellular growth pathways, showing efficacy in certain cancers. Additionally, kinase inhibitors such as ibrutinib, which targets Bruton tyrosine kinase, have been approved for specific malignancies, including mantle cell lymphoma. These treatments highlight the ongoing efforts to target protein synthesis and related pathways in cancer therapy.

What other types of research exist?

Promising novel alternatives to Zotatifin (eFT226) for solid tumor patients include: 1) Temsirolimus, an mTOR inhibitor, which has shown some promise in treating various cancers by inhibiting a key pathway regulating cellular growth and survival. 2) Everolimus, another mTOR inhibitor, which has demonstrated clinical benefits in combination with other agents like letrozole. 3) Evinacumab, a monoclonal antibody targeting ANGPTL3, which is under investigation for its potential to lower LDL-C and triglycerides, and may have implications in cancer treatment due to its role in lipid metabolism and cellular growth.

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Translation Inhibitor

Zotatifin for Solid Tumors (Zotatifin Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Effector Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

- Maximum of five prior lines of therapy for advanced/metastatic disease.

Patient has histological or cytological confirmation of breast cancer.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, approximately 12 months

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

No Placebo-Only Group

Summary

This trial is testing a new drug called Zotatifin for patients with advanced cancers that haven't improved with standard treatments. The drug works by stopping cancer cells from making essential proteins, which may slow or stop the cancer.

Who is the study for?

This trial is for adults with certain advanced solid tumors who've had previous treatments like CDK4/6 inhibitors and are now facing cancer that's resistant or intolerant to standard therapies. They should have tried at least one, but no more than five lines of therapy for metastatic disease, and specific criteria apply based on the type of tumor (ER+, HER2-, KRAS mutation, etc.).

What is being tested?

The study tests Zotatifin (eFT226) alongside other drugs like Abemaciclib, Fulvestrant, Trastuzumab, and Sotorasib in a Phase 1-2 trial. It aims to find out how safe eFT226 is and how it affects the body (pharmacokinetics/dynamics) as well as its effectiveness against various solid tumors.

What are the potential side effects?

Potential side effects may include typical reactions seen with cancer treatments such as nausea, fatigue, blood count changes leading to increased infection risk or bleeding problems. Specific drug-related side effects will be monitored closely due to the investigational nature of Zotatifin.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had no more than five treatments for my advanced cancer.

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My breast cancer diagnosis was confirmed through lab tests.

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I have been treated with a CDK4/6 inhibitor before.

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My tumor has a KRAS mutation, but not the G12C type.

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My tumor is estrogen receptor positive and not HER2 positive.

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I have been treated with platinum-based chemotherapy and anti-PD-1/L1 therapy.

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My tumor is estrogen receptor positive.

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My tumor is estrogen receptor positive.

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My cancer has spread or returned and doesn't respond to current treatments.

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My tumor shows high levels of Cyclin D1.

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My cancer has worsened after receiving a HER2-targeted therapy and chemotherapy.

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My lung cancer is at an advanced stage with fluid buildup or has spread.

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My cancer returned or worsened after hormone therapy for advanced disease.

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My tumor is estrogen receptor positive and has FGFR amplification.

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My tumor is positive for both estrogen receptors and HER2.

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My tumor has a specific KRAS mutation, and I haven't had KRAS-targeted therapy.

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I have received at least one treatment for my advanced cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, approximately 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, approximately 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, approximately 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 2: (Combination Cohorts) Determine MTD

Part 2: (Combination Cohorts) Determine RP2D

Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs

+7 more

Secondary study objectives

Evaluate plasma Pharmacokinetic (PK) parameters of eFT226

Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant

DNA Nucleotidylexotransferase

+7 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

11Treatment groups

Experimental Treatment

Group I: Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK)Experimental Treatment1 Intervention

Cohort EMNK

Group II: Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH)Experimental Treatment1 Intervention

Cohort EMBH

Group III: Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF)Experimental Treatment1 Intervention

Cohort EMBF

Group IV: Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS)Experimental Treatment1 Intervention

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

Group V: Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT)Experimental Treatment1 Intervention

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

Group VI: Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)Experimental Treatment2 Interventions

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

Group VII: Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF)Experimental Treatment1 Intervention

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

Group VIII: Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1Experimental Treatment1 Intervention

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

Group IX: Part 1b Dose Escalation, Combination, BreastExperimental Treatment1 Intervention

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

Group X: Part 1a: Dose Escalation, Combination, BreastExperimental Treatment1 Intervention

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

Group XI: Part 1: Sequential escalation (Completed)Experimental Treatment1 Intervention

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

First Studied

Drug Approval Stage

How many patients have taken this drug

Fulvestrant

FDA approved

Abemaciclib

FDA approved

Trastuzumab

FDA approved

Sotorasib

FDA approved

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors often target key processes involved in cancer cell growth and survival. For example, Zotatifin (eFT226) inhibits eukaryotic translation initiation factor 4A (eIF4A), disrupting protein synthesis and potentially reducing tumor growth and proliferation. Similarly, kinase inhibitors target specific enzymes involved in signaling pathways that regulate cell division and survival, while mTOR inhibitors interfere with a pathway crucial for cell growth and metabolism. These mechanisms are vital for solid tumor patients as they directly target the cellular processes that enable tumor growth, offering a strategic approach to limit cancer progression and improve patient outcomes.

Salubrinal in Combination With 4E1RCat Synergistically Impairs Melanoma Development by Disrupting the Protein Synthetic Machinery.Genetic and pharmacological inhibition of eIF4E effectively targets esophageal cancer cells and augments 5-FU's efficacy.Target-Based Screening against eIF4A1 Reveals the Marine Natural Product Elatol as a Novel Inhibitor of Translation Initiation with In Vivo Antitumor Activity.