ETX-636 for Cancer

Recruiting at 5 trial locations

Overseen By Melinda Snyder

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ensem Therapeutics

Disqualifiers: Other cancers, Brain metastases, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

233 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ETX-636, for individuals with advanced solid tumors. It evaluates the effectiveness of ETX-636 alone or in combination with fulvestrant, specifically targeting certain types of breast cancer. The trial seeks participants whose cancer has progressed after previous treatments and who have a specific genetic change known as a PIK3CA mutation. Ideal candidates include those with advanced breast cancer that cannot be surgically removed and have not responded to other therapies. As a Phase 1, Phase 2 trial, this research aims to understand how ETX-636 works in people and measure its effectiveness in an initial group, offering participants a chance to be among the first to benefit from this new treatment.

Do I need to stop taking my current medications for the trial?

The trial requires that you stop any local or systemic anticancer therapy or investigational anticancer agent at least 14 days before starting the treatment. It doesn't specify about other medications, so you should discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that ETX-636 holds promise in treating advanced solid tumors. It targets specific gene changes that can make cancer more aggressive, offering hope for hard-to-treat cancers.

Early research suggests that ETX-636 might reduce the risk of high blood sugar, a common side effect of similar treatments. The FDA has fast-tracked ETX-636 for certain types of breast cancer, indicating that the potential benefits may outweigh the risks for these conditions.

Researchers are studying ETX-636 in combination with fulvestrant, a drug used for certain breast cancers, to assess its effectiveness and safety. While detailed information on side effects in these trials isn't available yet, the treatment's Phase 1/2 status means researchers are still closely monitoring its safety.

Overall, while specific safety data is still being collected, the ongoing trials and fast-track status suggest cautious optimism about ETX-636's safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ETX-636 because it targets cancer in a unique way. Unlike most standard treatments for advanced solid tumors and HR+/HER2- breast cancer, which often involve chemotherapy or hormone therapies, ETX-636 is a pan-mutant-selective PI3Kα inhibitor. This means it specifically targets and inhibits a mutated form of the PI3Kα enzyme that's often implicated in cancer growth. By focusing on this specific mutation, ETX-636 has the potential to more effectively stop cancer progression with potentially fewer side effects than broader-acting treatments. This targeted approach could offer a new hope for patients, particularly those with cancers that have been resistant to existing therapies.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that ETX-636 is a promising treatment for certain cancers. This drug targets specific changes in cancer cells, particularly those with PIK3CA mutations. Early lab studies demonstrated that ETX-636 effectively blocked cancer growth, leading to tumor shrinkage. In this trial, some participants will receive ETX-636 as a monotherapy for advanced solid tumors with PIK3CA mutation. Others will receive ETX-636 combined with fulvestrant, a common treatment for some breast cancers, which may be particularly helpful for treating advanced breast cancer that is hormone receptor-positive and HER2-negative. The FDA has fast-tracked this combination, indicating its potential to meet important medical needs. Overall, early evidence suggests ETX-636 could effectively treat advanced cancers with specific genetic changes. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including breast cancer, that have a specific mutation (PIK3CA). Participants must have tried other treatments like CDK4/6 inhibitors and anti-estrogen therapy without success. They should be relatively active and well (ECOG score 0 or 1) and have at least one measurable tumor.

Inclusion Criteria

Key

I have at least one tumor that can be measured.

My cancer has spread and cannot be removed by surgery, and it has worsened after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment Part A

Participants receive escalating doses of ETX-636 as monotherapy for advanced solid tumors with PIK3CA mutation

28 days per cycle

Treatment Part B

Participants receive escalating doses of ETX-636 in combination with fulvestrant for HR+/HER2- breast cancer

28 days per cycle

Treatment Part C

Combination therapy expansion with ETX-636 and fulvestrant for HR+/HER2- breast cancer

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• ETX-636

Trial Overview The study is testing different doses of ETX-636 alone or in combination with fulvestrant, an existing breast cancer treatment. It's an early-phase trial to see how safe the drug is and how it affects people with certain types of advanced cancers.

How Is the Trial Designed?

Group I: Part C Dose Expansion Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer) Experimental Treatment 1 Intervention

Part B is a dose expansion combination therapy in HR+/HER2- locally advanced or metastatic breast cancer. The study treatment will be ETX-636, a pan-mutant-selective PI3Kα inhibitor, in combination with fulvestrant (Faslodex) at a fixed dose of 500 mg IM.

Group II: Part B Dose Escalation Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer) Experimental Treatment 1 Intervention

Part B is a dose escalation combination therapy in HR+/HER2- locally advanced or metastatic breast cancer. The study treatment will be ETX-636, a pan-mutant-selective PI3Kα inhibitor, in combination with fulvestrant (Faslodex) at a fixed dose of 500 mg IM.

Group III: Part A Dose Escalation Monotherapy (Advanced Solid Tumors with PIK3CA mutation) Experimental Treatment 1 Intervention

Part A is a dose escalation monotherapy of ETX-636 in advanced solid tumors with PIK3CA mutation

Who Is Running the Clinical Trial?

Ensem Therapeutics

Lead Sponsor

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06993844

NCT06993844 | Phase 1/2 Study of ETX-636 in ... Brief Summary: This is a Phase 1/2, open-label, multicenter, 3-part study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of ETX-636 ...

2. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-etx-636-for-pik3ca-mutant-hr-her2-negative-breast-cancer

FDA Grants Fast Track Designation to ETX-636 for PIK3CA ... ETX-636 targets PI3Kα mutations in HR-positive, HER2-negative advanced breast cancer, offering potential therapeutic advantages over non-mutant ...

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/1659/756556/Abstract-1659-ETX-636-a-novel-allosteric-pan

ETX-636, a novel allosteric pan-mutant-selective PI3Kα dual ... ETX-636 dosed orally, once daily, results in deep and durable pathway inhibition and induces tumor regression in kinase and helical domain ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1086

Updated efficacy of mutant-selective PI3Kα inhibitor RLY- ... Plasma mutational burden in PIK3CA and TP53 independently predicts early progression in patients with HR+/HER2- metastatic breast cancer (MBC) ...

5. cancernetwork.com cancernetwork.com/view/fda-grants-fast-track-designation-to-novel-pik3-inhibitor-in-breast-cancer

FDA Grants Fast Track Designation to Novel PIK3α ... Combination therapy of ETX-636 plus fulvestrant is being administered to patients with HR–positive, HER2-negative breast cancer in a phase 1/2 ...

6. targetedonc.com targetedonc.com/view/fda-fast-tracks-etx-636-in-pik3ca-mutant-hr-breast-cancer

FDA Fast-Tracks ETX-636 in PIK3CA-Mutant, HR+ Breast ... FDA fast tracks ETX-636, a promising treatment for advanced breast cancer with PIK3CA mutations, aiming to improve patient outcomes.

7. firstwordpharma.com firstwordpharma.com/story/6229176

Ensem Therapeutics Announces ETX-636 Granted Fast ... “Patients with advanced HR+/HER2- breast cancer harboring PIK3CA mutations have poor prognosis, and there is an unmet need for therapies ...