RGT-490 for adults with PIK3CA-mutated advanced solid tumors

A Phase 1/1b Open-Label, Multicenter, First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of RGT-490 as a Single Agent in Adult Subjects With Locally Advanced or Metastatic PIK3CA-Mutated Solid Tumors Including HR+/HER2- Breast Cancers

This trial will test RGT-490, an oral medicine, in adults whose advanced solid tumors carry a PIK3CA mutation and have progressed after prior therapy.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 63 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Regor Pharmaceuticals Inc. (industry)
• Locations: 3 sites (Houston, Texas and 2 other locations)
• Trial ID: NCT07524322 on ClinicalTrials.gov

What this trial studies

This phase 1/1b, open-label, multicenter study uses sequential parts (dose-escalation followed by expansion cohorts) to characterize the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of oral RGT-490 in adults with locally advanced or metastatic solid tumors that harbor activating PIK3CA alterations. Eligible participants have measurable or evaluable disease per RECIST v1.1, an ECOG performance status of 0–1, and adequate organ function, and must have progressed on or after at least one available therapy. Key exclusions include prior PI3Kα inhibitor therapy, diabetes requiring anti-hyperglycemic medication, and uncontrolled or symptomatic CNS metastases. Sites for enrollment are in Houston and San Antonio, Texas, and Fairfax, Virginia, with dosing and safety/efficacy assessments conducted according to protocol schedules.

Who should consider this trial

Good fit: Adults with unresectable or metastatic solid tumors that harbor a documented activating PIK3CA mutation, have progressed after at least one prior therapy, have measurable or evaluable disease, ECOG 0–1, and adequate organ function are ideal candidates.

Not a fit: Patients without a PIK3CA mutation, those who received prior PI3Kα inhibitors, those with diabetes requiring anti-hyperglycemic drugs, or those with uncontrolled symptomatic CNS metastases are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, RGT-490 could shrink tumors or slow disease progression in patients whose cancers are driven by PIK3CA mutations.

How similar studies have performed: Similar targeted approaches have precedent—PI3Kα inhibitors such as alpelisib have shown benefit in PIK3CA-mutant breast cancer—so the mechanism has demonstrated activity though toxicity and resistance remain concerns.

Eligibility criteria

Inclusion Criteria:

* Adults with metastatic or locally advanced, unresectable solid tumors that have progressed on or after at least one available therapy.
* Presence of one or more documented activating PIK3CA mutation in tumor tissue and/or blood.
* At least 1 measurable lesion or evaluable disease per RECIST v1.1.
* An ECOG performance status of 0 or 1.
* Adequate organ function

Exclusion Criteria:

* Diabetes mellitus requiring anti-hyperglycemic medication.
* Prior treatment with PI3Kα inhibitors
* Symptomatic, untreated, or uncontrolled central nervous system metastases.
* Receipt of any local or systemic anticancer therapy or investigational anticancer agent within a protocol-defined washout period prior to study treatment.
* Unresolved clinically significant toxicities from prior anticancer therapy
* History of a another malignancy within 2 years prior to screening (exception adequately treated cancers).

Where this trial is running

Houston, Texas and 2 other locations

• NEXT Houston — Houston, Texas, United States (RECRUITING)
• NEXT San Antonio — San Antonio, Texas, United States (RECRUITING)
• NEXT Virginia — Fairfax, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Sarah Wheeler

Conditions: Breast Cancer, Ovarian Cancer, Endometrial Cancer, PIK3CA Mutation, HER2- Negative Breast Cancer, Advanced Breast Cancer, Unresectable Solid Tumor, Hormone Receptor Positive Tumor