Solid Tumors
Conditions
Keywords
PIK3CA-H1047R, Cancer
Brief summary
The study is designed to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of REC-7735 in participants with unresectable, locally advanced, or metastatic PIK3CA-H1047R mutated solid tumors.
Interventions
DRUGREC-7735
Oral
Sponsors
Recursion Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants have histologically-confirmed unresectable, locally advanced, or metastatic solid tumors which exhibit the PIK3CA H1047R mutation in tumor tissue and/or blood (circulating tumor deoxyribonucleic acid \[ctDNA\]). * For Phase 1A and planned monotherapy cohorts in Phase 1B, participants have experienced progressive disease, relapsed disease, or be intolerant to at least one established standard systemic anti-cancer treatment for a given tumor type, or in the opinion of the Investigator have been considered ineligible for standard therapy. * All toxicities from prior anti-cancer therapies have resolved to ≤ Grade 1 or the participant's previous baseline, with the exception of alopecia and peripheral neuropathy. Key
Exclusion criteria
* Participants have experienced disease progression with a phosphoinositide 3-kinase (PI3Ka), protein kinase B (AKT) or mechanistic target of rapamycin (mTOR) inhibitor unless deemed suitable for REC-7735 treatment at the discretion of the Investigator and following discussion with the Sponsor. * Known loss-of-function mutations in phosphatase and tensin homolog (PTEN), PTEN loss, or activating mutations in AKT, unless deemed suitable for REC-7735 treatment at the discretion of the Investigator and following discussion with the Sponsor. * Major surgery within 6 weeks from treatment initiation. * Any serious underlying medical or psychiatric condition that would preclude understanding and rendering of informed consent or impair the ability of the participant to receive or tolerate the planned treatment. * Recent or ongoing serious infection. * Recent prior systemic anti-cancer treatment. * Known clinically significant UGT1A1 deficiency, including Gilbert's syndrome (for example, documented homozygous UGT1A1\*28) * Has an established diagnosis of uncontrolled diabetes mellitus defined as meeting any one of the following: NOTE: This criterion is not applicable to those participants enrolling in the Phase 1B Dose Expansion cohort designated for hyperglycemia vulnerable participants * Glycated hemoglobin (HbA1c) ≥8% * Currently requiring insulin * Fasting blood glucose (FBG) ≥140 milligrams (mg)/deciliter (dL) (7.8 millimoles \[mmol\]/liter \[L\]) in the past 30 days prior to dosing NOTE: Two FBG samples must be drawn at least seven days apart from each other. Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1A: Number of Participants With Dose-limiting Toxicities (DLTs) | 28 days |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 2 years |
| Phase 1B: Objective Response Rate (ORR) According to Standard Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Up to 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Maximum (Peak) Drug Concentration (Cmax) of REC-7735 | Up to 2 years |
| Time to Reach Cmax following drug administration (Tmax) of REC-7735 | Up to 2 years |
| Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of REC-7735 | Up to 2 years |
| Phase 1A: ORR According to Standard RECIST 1.1 | Up to 2 years |
| Phase 1B: Clinical Benefit Rate (CBR) According to Standard RECIST 1.1 | Up to 2 years |
| Phase 1B: Duration of Response (DOR) According to Standard RECIST 1.1 | Up to 2 years |
| Phase 1B: Duration of Stable Disease (SD) According to Standard RECIST 1.1 | Up to 2 years |
| Phase 1B: Time to Response (TTR) According to Standard RECIST 1.1 | Up to 2 years |
| Phase 1B: Progression-free Survival (PFS) According to Standard RECIST 1.1 | Up to 2 years |
| Phase 1B: Overall Survival | Up to 2 years |
Countries
United States
Contacts
CONTACTRecursion Pharmaceuticals
Outcome results
None listed