Title
A First-in-Human Study of Mutant-selective PI3Ka; Inhibitor, RLY-2608, as a Single Agent in Patients with Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer

Description
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-2608, in advanced solid tumor patients with a Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in blood and/or tumor per local assessment. The study will evaluate both RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors and RLY-2608 + fulvestrant combination arm for patients with HR+ HER2- locally advanced or metastatic breast cancer. This study consists of 2 parts, a dose escalation (Part 1) and a dose expansion (Part 2).

Objective
Primary RLY-2608 Single Agent Arm:
-To determine the MTD and RP2D of RLY-2608 as single agent
-To determine the safety and tolerability of RLY-2608 as single agent

Primary RLY-2608 + Fulvestrant Arm:
-To determine the MTD and RP2D of RLY-2608 in combination with fulvestrant
-To determine the safety and tolerability of RLY-2608 in combination with fulvestrant

Secondary RLY-2608 Single Agent Arm:
-To evaluate PIK3CA genotype in blood and tumor tissue by next-generation nucleic acid sequencing
-To define the PK profile of RLY-2608 (and its metabolites, as appropriate) as single agent
-To assess the potential impact of RLY-2608 single agent on glucose metabolism
-To assess the potential impact of RLY-2608 single agent on pharmacodynamic markers in blood and tumor tissue
-To characterize the preliminary antitumor activity of RLY-2608 as single agent

Secondary RLY-2608 + Fulvestrant Arm:
- To evaluate PIK3CA genotype in blood and tumor tissue by next-generation nucleic acid sequencing
-To define the PK profile of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant
-To assess the potential impact of RLY-2608 in combination with fulvestrant on glucose metabolism
-To assess the potential impact of RLY-2608 in combination with fulvestrant on pharmacodynamic markers in blood and tumor tissue
-To characterize the preliminary antitumor activity of RLY-2608 in combination with fulvestrant

Treatment Experimental: RLY-2608 for patients with unresectable or metastatic solid tumors
Multiple doses of RLY-2608 for oral administration.
Experimental: RLY-2608 + fulvestrant combination for HR+ HER2- locally advanced or metastatic breast cancer
Oral dose of RLY-2608 in addition to fulvestrant as determined during Part 1 Dose Escalation.

Key Eligibility For full subject eligibility, see this study's clinicaltrials.gov record.

Applicable Disease Sites
Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital