A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation

Conditions

• CLOVES Syndrome
• Klippel Trenaunay Syndrome
• Lymphatic Malformations
• Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP)
• PIK3CA Mutation
• PIK3CA-Related Overgrowth Spectrum (PROS)
• Vascular Malformations

Eligibility Criteria

Sex

ALL

Age

2 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• RLY-2608 — DRUG
  RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
• Placebo — DRUG
  RLY-2608 matched-placebo

Study Details

This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, RLY-2608, in adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and malformations driven by PIK3CA mutation. Part 1 is a dose selection, Part 2 is a basket design with exploratory single-arm cohorts for various subpopulations of participants, and Part 3 is randomized, double-blinded study vs placebo.

Key Dates

Start date

Jun 13, 2025

Status verified

Apr 2026

Primary completion

Jul 31, 2031

Completion

Oct 31, 2031

Study Design

Enrollment

277 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Part 1, Group 1
  RLY-2608 for patients ≥12 years old with PROS or malformations with PIK3CA mutation. Multiple doses of RLY-2608 for oral administration.
• Experimental: Part 1, Group 2
  RLY-2608 for participants 6 to \<12 years old with PROS or malformations with PIK3CA mutation. RLY-2608 will be studied in pediatric participants in a dose escalation design.
• Experimental: Part 1, Group 3
  Part 1, Group 3: RLY-2608 for participants 2 to \<6 years old with PROS or malformations with PIK3CA mutation. RLY-2608 will be studied in pediatric participants in a dose escalation design.
• Experimental: Part 2, Group 1
  Dose expansion single-arm cohorts for various subpopulations of participants ≥12 years old with PROS or malformations with PIK3CA mutation. Oral dose of RLY-2608 as determined during Part 1.
• Experimental: Part 2, Group 2
  Dose expansion cohorts for participants 6 to \<12 years old with PROS or malformations with PIK3CA mutation. Oral dose of RLY-2608 as determined during Part 1.
• Experimental: Part 2, Group 3
  Dose expansion cohorts for participants 2 to \<6 years old with PROS or malformations with PIK3CA mutation. Oral dose of RLY-2608 as determined during Part 1.
• Experimental: Part 3, Arm 1
  Adult (\>18 yo), and adolescent and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive RLY-2608 at oral dose determined during Part 1/2 versus placebo.
• Placebo Comparator: Part 3, Arm 2
  Adult (\>18 yo), and adolescent, and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive placebo.

Primary Outcome Measure

Parts 1 and 2: Determination of a recommended phase 2 dose RP2D(s) for Groups 1, 2, and 3 [ Time Frame: Cycle 1 of treatment and at the end of every cycle until study discontinuation ]

Central Contacts

• Relay Therapeutics, Inc
  617-322-0731
  [email protected]

Locations (19)

Find similar trials in Phoenix, AZ

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