A First-in-Human Study of Mutant-selective PI3Ka Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer

Eligibility: Inclusion Criteria
  •   Key Inclusion Criteria
  •   Patient has ECOG performance status of 0-1
  •   One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment
  •   - Other potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment.
  •   Part 1 - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively.
  •   Key Inclusion for RLY-2608 Single Agent Arm
  •   [For Part 1]: Evaluable disease per RECIST v1.1
  •   [For Part 2]: Measurable disease per RECIST v1.1
  •   Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy.
  •   Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor
  •   Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types:
  •   Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid tumors with PIK3CA double mutations
  •   Key Inclusion for RLY-2608 + Fulvestrant Arm
  •   [For Part 1 and Part 2]: Evaluable disease per RECIST v1.1
  •   Male or postmenopausal female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative therapy and must have been previously treated with GnRH agonist at least 4 weeks prior to start of study drug
  •   [For Part 1 and Part 2]: Had previous treatment for advanced or metastatic breast cancer with:
  •   =1 chemotherapy regimen,
  •   >=1 cyclin-dependent kinases (CDK) 4/6 inhibitor, and
  •   >=1 antiestrogen therapy including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and
  •   >=1 PARP inhibitor if documented germline BRCA1/2 mutation Note: Chemotherapy for local or loco-regional treatment is not included in enumeration or previous treatment
  •   [For Part 2, Group 2]: Received prior treatment with a PI3K¿ inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.
  •   Key
Exclusion Criteria
  •   Prior treatment with PI3K¿ inhibitors (except for RLY-2608 + fulvestrant arm, Part 2, Group 2).
  •   Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose >=140 mg/dL and glycosylated hemoglobin (HbA1c) >=7.0%.
  •   History of hypersensitivity to PI3K inhibitors
  •   QT interval corrected using Fridericia's formula (QTcF) > 480 msec or history of prolonged QT syndrome, Torsades de pointes or familial history of prolonged QT syndrome Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms