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
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.
Arms & interventions
- DrugRGT-490
Oral tablets
Outcome measures
Primary
Incidence of dose limiting toxicities (DLTs)
Number of subjects who experience at least 1 Dose Limiting Toxicity (DLT)
Time frame: 4 weeks (1 cycle)
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs)
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)
Time frame: Every cycle (4-week cycles) until study discontinuation, approximately 12 months
Secondary
Characterize the Cmax (PK) of RGT-490 monotherapy in Dose Escalation
Time frame: First 3 treatment cycles (each cycle is 28 days)
Characterize the Tmax (PK) of RGT-490 monotherapy in Dose Escalation
Time frame: First 3 treatment cycles (each cycle is 28 days)
Characterize the AUC (PK) of RGT-490 monotherapy in Dose Escalation
Time frame: First 3 treatment cycles (each cycle is 28 days)
Measure PD effects of RGT-490 monotherapy in Dose Escalation and Phase 1b
Time frame: First 7 cycles (each cycle is 28 days) and at study discontinuation
Changes in fasting blood glucose
Time frame: 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)
Time frame: 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
Time frame: Approximately every 8 weeks until progressive disease, approximately 12 months
Evaluate additional measures of efficacy of RGT-490
Time frame: Approximately every 8 weeks until progressive disease, approximately 36 months
Evaluate additional measures of efficacy of RGT-490
Time frame: Approximately every 8 weeks until progressive disease, approximately 36 months
Eligibility criteria
Study locations (4)
START Los Angeles
Los Angeles, California, 90025
NEXT Houston
Houston, Texas, 77054
NEXT San Antonio
San Antonio, Texas, 78229
NEXT Virginia
Fairfax, Virginia, 22031