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
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Regor Pharmaceuticals Inc.
- Enrollment
- 63
- Locations
- 3
- Primary Endpoint
- Incidence of dose limiting toxicities (DLTs)
Overview
Brief Summary
This is a phase 1/1b, open-label, multicenter study consisting of sequential parts designed to evaluate the safety, tolerability, and effects pharmacokinetic (PK) profile, and antitumor activity of RGT-490, an investigational oral therapy, in adults with locally advanced or metastatic solid tumors including breast cancer.
Participants enrolled in the study have advanced disease that is not amendable to curative treatment and whose tumors harbor alterations in the PI3KCA gene.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •An ECOG performance status of 0 or
- •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).
Arms & Interventions
Phase 1 Dose Escalation (Advanced Solid Tumors with PIK3CA mutation)
RGT-490 given alone as monotherapy
Intervention: RGT-490 (Drug)
Phase 1b Dose Expansion (HR+/HER2- locally advanced or metastatic breast cancer)
RGT-490 given alone as monotherapy
Intervention: RGT-490 (Drug)
Outcomes
Primary Outcomes
Incidence of dose limiting toxicities (DLTs)
Time Frame: 4 weeks (1 cycle)
Number of subjects who experience at least 1 Dose Limiting Toxicity (DLT)
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Every cycle (4-week cycles) until study discontinuation, approximately 12 months
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) and AEs leading to dose modifications and dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
Secondary Outcomes
- Characterize the Cmax (PK) of RGT-490 monotherapy in Dose Escalation(First 3 treatment cycles (each cycle is 28 days))
- Characterize the Tmax (PK) of RGT-490 monotherapy in Dose Escalation(First 3 treatment cycles (each cycle is 28 days))
- Characterize the AUC (PK) of RGT-490 monotherapy in Dose Escalation(First 3 treatment cycles (each cycle is 28 days))
- Measure PD effects of RGT-490 monotherapy in Dose Escalation and Phase 1b(First 7 cycles (each cycle is 28 days) and at study discontinuation)
- Changes in fasting blood glucose(Approximately every week in Cycle 1 and Cycle 2 (4-week cycle), every 2 weeks in Cycles 3-6 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months)
- Changes in longitudinal glucose metabolism (All Phases)(Approximately every cycle (4-week cycles) until study discontinuation, approximately 24 months)
- Assess preliminary efficacy of RGT-490 monotherapy in dose escalation and Phase 1b(Approximately every 8 weeks until progressive disease, approximately 12 months)
- Evaluate additional measures of efficacy of RGT-490(Approximately every 8 weeks until progressive disease, approximately 36 months)