Health Trials

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 (The ReInspire Study)

ConditionsPIK3CA-Related Overgrowth Spectrum (PROS)Lymphatic MalformationsVascular MalformationsPIK3CA MutationCLOVES SyndromeKlippel Trenaunay SyndromeMegalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP)Vascular Anomalies
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age2+
SponsorRelay Therapeutics, Inc.

About this trial

This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, zovegalisib (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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA classification.

One or more documented activating PIK3CA mutation(s) that are targeted by selective PI3Kα inhibitors in lesional tissue and/or cell-free DNA from the lesion or blood. Some participants may be eligible without a documented PIK3CA mutation, with the sponsor's approval, as long as no other genetic driver has been documented.

Lansky (<16 yo) or Karnofsky (≥16 yo) performance status of ≥50.

Agree to provide archived lesional fluid and/or tissue or be willing to undergo pretreatment lesional biopsy (if considered safe and medically feasible) to assess PIK3CA status.

Disqualifiers

Known hypersensitivity to RLY-2608.

Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

Clinically significant, uncontrolled cardiovascular disease

Systemic therapy or antibody within 5 half-lives of the therapy.

Trial design

Design model

Parallel

Treatments tested in this trial

  • RLY-2608

    Drug

    RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

  • Placebo

    Drug

    RLY-2608 matched-placebo

Treatment groups

277 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Part 1, Group 1Experimental treatment 1 intervention
Group B: Part 1, Group 2Experimental treatment 1 intervention
Group C: Part 1, Group 3Experimental treatment 1 intervention
Group D: Part 2, Group 1Experimental treatment 1 intervention
Group E: Part 2, Group 2Experimental treatment 1 intervention
Group F: Part 2, Group 3Experimental treatment 1 intervention
Group G: Part 3, Arm 1Experimental treatment 1 intervention
Group H: Part 3, Arm 2Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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
2

Parts 1 and 2: Occurrence/frequency of Adverse Events (AEs), changes in vital signs, ECGs, and safety laboratory tests and their relationship to the study drugs (safety and tolerability).

Time frame
Cycle 1 of treatment and at the end of every cycle until study discontinuation
3

Part 3: Percentage of participants with volumetric Response.

Time frame
Baseline, Week 24

Secondary outcomes

1

Part 1 and 2: Percent change from baseline in lesion volume

Time frame
Baseline, Week 24
2

Part 1 and 2: Duration of response, defined as the time of first documented response to the date of first documented disease progression or death due to any cause

Time frame
Approximately every 3 months for approximately the first year, and then every 6 months during treatment
3

Part 1 and 2: Percentage of participants with volumetric response

Time frame
Baseline, week 12, week 24
4

Part 1 and 2: Plasma concentrations and PK parameters of RLY-2608

Time frame
Approximately every 2 weeks in Cycle 1, then again at Cycles 2, 4 and Cycle 7 depending on the participant's group

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Relay Therapeutics, Inc.

Lead sponsor

Source ClinicalTrials.gov
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