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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05216432




Registration number
NCT05216432
Ethics application status
Date submitted
20/12/2021
Date registered
31/01/2022

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
RLY-2608-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PIK3CA Mutation 0 0
Solid Tumor, Adult 0 0
HER2-negative Breast Cancer 0 0
Breast Cancer 0 0
Metastatic Breast Cancer 0 0
Advanced Breast Cancer 0 0
Unresectable Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RLY-2608
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Palbociclib 125mg
Treatment: Drugs - Ribociclib 400mg
Treatment: Drugs - Ribociclib 600mg

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.

Experimental: RLY-2608+fulvestrant+palbociclib 125 mg for HR+ HER2- locally advanced or metastatic breast cancer - Oral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation.

Experimental: RLY-2608+fulvestrant+ribociclib 400 mg for HR+ HER2- locally advanced or metastatic breast cancer - Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation.

Experimental: RLY-2608+fulvestrant+ribociclib 600 mg for HR+ HER2- locally advanced or metastatic breast cancer - Oral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation.


Treatment: Drugs: RLY-2608
RLY-2608 is a mutant-selective, oral PI3Ka inhibitor.

Treatment: Drugs: Fulvestrant
500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).

Treatment: Drugs: Palbociclib 125mg
125mg palbociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

Treatment: Drugs: Ribociclib 400mg
400mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

Treatment: Drugs: Ribociclib 600mg
600mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 as a single agent
Timepoint [1] 0 0
Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Primary outcome [2] 0 0
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant
Timepoint [2] 0 0
Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Primary outcome [3] 0 0
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant and a CDK 4/6 inhibitor (palbociclib, ribociclib)
Timepoint [3] 0 0
Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Primary outcome [4] 0 0
Number of patients with adverse events and serious adverse events of RLY-2608 as a single agent
Timepoint [4] 0 0
Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Primary outcome [5] 0 0
Number of patients with adverse events and serious adverse events of RLY-2608 in combination with fulvestrant
Timepoint [5] 0 0
Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Primary outcome [6] 0 0
Number of patients with adverse events and serious adverse events of RLY-2608 in combination with fulvestrant and a CDK 4/6 inhibitor (palbociclib, ribociclib)
Timepoint [6] 0 0
Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Secondary outcome [1] 0 0
PIK3CA gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue
Timepoint [1] 0 0
Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [2] 0 0
Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) as single agent
Timepoint [2] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [3] 0 0
Pharmacokinetic parameters including area under the plasma concentration versus time curve during a dose interval (AUC0-tau) of RLY-2608 (and its metabolites, as appropriate) as single agent
Timepoint [3] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [4] 0 0
Pharmacokinetic parameters including half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) as single agent
Timepoint [4] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [5] 0 0
Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant
Timepoint [5] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [6] 0 0
Pharmacokinetic parameters including area under the plasma concentration versus time curve during a dose interval (AUC0-tau) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant
Timepoint [6] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [7] 0 0
Pharmacokinetic parameters including half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant
Timepoint [7] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [8] 0 0
Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib)
Timepoint [8] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [9] 0 0
Pharmacokinetic parameters including area under the plasma concentration vs time curve of RLY-2608 (and its metabolites, as appropriate) administered with fulvestrant and CDK4/6 inhibitor (palbociclib, ribociclib)
Timepoint [9] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [10] 0 0
Pharmacokinetic parameters including half-life (t1/2) of RLY-2608 (and its metabolites, as appropriate) when RLY-2608 is administered in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib)
Timepoint [10] 0 0
Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through end of treatment, approximately 24 months
Secondary outcome [11] 0 0
Changes in circulating blood of fasting glucose in RLY-2608 as a single agent
Timepoint [11] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [12] 0 0
Changes in circulating blood of insulin in RLY-2608 as a single agent
Timepoint [12] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [13] 0 0
Changes in circulating blood of C-peptide in RLY-2608 as a single agent
Timepoint [13] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [14] 0 0
Changes in circulating blood of HbA1c in RLY-2608 as a single agent
Timepoint [14] 0 0
Once in Cycle 2 (4-week cycle) and then once every 3rd cycle beginning with Cycle 5 through end of treatment, approximately 24 months
Secondary outcome [15] 0 0
Changes in circulating blood of fasting glucose in RLY-2608 in combination with fulvestrant
Timepoint [15] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [16] 0 0
Changes in circulating blood of insulin in RLY-2608 in combination with fulvestrant
Timepoint [16] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [17] 0 0
Changes in circulating blood of C-peptide in RLY-2608 in combination with fulvestrant
Timepoint [17] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [18] 0 0
Changes in circulating blood of HbA1c in RLY-2608 in combination with fulvestrant
Timepoint [18] 0 0
Once in Cycle 2 (4-week cycle) and then once every 3rd cycle beginning with Cycle 5 through end of treatment, approximately 24 months
Secondary outcome [19] 0 0
Changes in circulating blood of fasting glucose in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib)
Timepoint [19] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [20] 0 0
Changes in circulating blood of insulin in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib)
Timepoint [20] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [21] 0 0
Changes in circulating blood of C-peptide in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib)
Timepoint [21] 0 0
Approximately every week in Cycle 1 (4-week cycle), every two weeks in Cycle 2 (4-week cycle), and every cycle starting with Cycle 3 through end of treatment, approx 24 months
Secondary outcome [22] 0 0
Changes in circulating blood of HbA1c in RLY-2608 in combination with fulvestrant and a CDK4/6 inhibitor (palbociclib, ribociclib)
Timepoint [22] 0 0
Once in Cycle 2 (4-week cycle) and then once every 3rd cycle beginning with Cycle 5 through end of treatment, approximately 24 months
Secondary outcome [23] 0 0
Objective response rate (ORR) as assessed by RECIST v1.1
Timepoint [23] 0 0
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Secondary outcome [24] 0 0
Duration of Response (DOR) as assessed by RECIST v1.1
Timepoint [24] 0 0
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Secondary outcome [25] 0 0
Disease Control Rate (DCR) as assessed by RECIST v1.1
Timepoint [25] 0 0
Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months
Secondary outcome [26] 0 0
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30)
Timepoint [26] 0 0
Once every cycle (4-week cycles) through end of treatment, approximately 24 months
Secondary outcome [27] 0 0
Clinical benefit rate (CBR) as assessed by RECIST v1.1
Timepoint [27] 0 0
[Time Frame: Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months]

Eligibility
Key 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 Combination Arms

* [For Part 1 and Part 2]: Evaluable disease per RECIST v1.1
* [For Part 1 and Part 2]: Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Females may be postmenopausal, premenopausal, or perimenopausal. 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 breast cancer with:

1. =1 line of chemotherapy in the metastatic setting
2. =1 cyclin-dependent kinases (CDK) 4/6 inhibitor, in either the adjuvant and/or metastatic setting
3. =1 antiestrogen therapy in either adjuvant and/or metastatic setting, 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
4. =1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment

[For RLY-2608 + fulvestrant arm; Part 2, Group 2]: Received prior treatment with a PI3Ka 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Prior treatment with PI3Ka, AKT, or mTOR 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. For combination arms only: hypersensitivity to fulvestrant, palbociclib, and/or ribociclib, as appropriate for the combination.

For triple combination arms only: history of pneumonitis or interstitial lung disease.

For the single agent and combination arms other than with ribociclib: mean QT interval corrected using Fridericia's formula (QTcF) >480 msec. For the combination arms with ribociclib: mean QTcF =450 msec.

Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a familial history of prolonged QT syndrome.

Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2026
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincents Hospital - Sydney
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2019 - Sydney
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux Cedex
Country [17] 0 0
France
State/province [17] 0 0
Villejuif
Country [18] 0 0
Italy
State/province [18] 0 0
Milano
Country [19] 0 0
Spain
State/province [19] 0 0
Catalonia
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Relay Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Relay Therapeutics Inc
Address 0 0
Country 0 0
Phone 0 0
617-322-0731
Fax 0 0
Email 0 0
ClinicalTrials@relaytx.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05216432