Advanced Breast Cancer, Breast Cancer, Cervical Cancer, Endometrial Cancer, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Ovarian Cancer, PIK3CA Mutation, Unresectable Solid Tumor
Conditions
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.
Interventions
DRUGRGT-490
Oral tablets
Sponsors
Regor Pharmaceuticals Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 v1.1. * 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Characterize the Cmax (PK) of RGT-490 monotherapy in Dose Escalation | First 3 treatment cycles (each cycle is 28 days) | Maximum observed plasma concentration (Cmax) of RGT-490 |
| Characterize the Tmax (PK) of RGT-490 monotherapy in Dose Escalation | First 3 treatment cycles (each cycle is 28 days) | Maximum observed plasma concentration (Tmax) of RGT-490 |
| Characterize the AUC (PK) of RGT-490 monotherapy in Dose Escalation | First 3 treatment cycles (each cycle is 28 days) | Calculated area under the plasma concentration curve (AUC) of RGT-490 |
| 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 | Change from baseline in ctDNA levels; Change from baseline in PD markers in paired biopsies |
| 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 | Measured by fasting blood glucose |
| Changes in longitudinal glucose metabolism (All Phases) | Approximately every cycle (4-week cycles) until study discontinuation, approximately 24 months | Measured by HbA1c |
| Assess preliminary efficacy of RGT-490 monotherapy in dose escalation and Phase 1b | Approximately every 8 weeks until progressive disease, approximately 12 months | Objective response rate (ORR) based on RECIST v1.1 |
| Evaluate additional measures of efficacy of RGT-490 | Approximately every 8 weeks until progressive disease, approximately 36 months | Duration of response (DoR) according to RECIST v1.1 |
Countries
United States
Contacts
CONTACTSarah Wheeler
CONTACTRegor Pharmaceuticals Central Office
Outcome results
None listed