REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors
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| ClinicalTrials.gov Identifier: NCT04526106 |
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Recruitment Status :
Recruiting
First Posted : August 25, 2020
Last Update Posted : December 22, 2022
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Sponsor:
Relay Therapeutics, Inc.
Information provided by (Responsible Party):
Relay Therapeutics, Inc.
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Brief Summary:
This is a Phase 1/2, open-label, FIH study designed to evaluate the safety, tolerability, PK, PDy, and antineoplastic activity of RLY-4008, a potent and highly selective FGFR2 inhibitor, in patients with unresectable or metastatic CCA and other solid tumors. The study consists of 3 parts: a dose escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| FGFR2 Amplification FGFR2 Gene Mutation FGFR2 Gene Fusion/Rearrangement FGFR2 Gene Translocation FGFR2 Gene Activation Intrahepatic Cholangiocarcinoma Cholangiocarcinoma Other Solid Tumors, Adult | Drug: RLY-4008 | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 400 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Part 1 (multiple ascending doses): • Unresectable or metastatic CCA or other unresectable or metastatic solid tumor Part 2 (RP2D determined in Part 1):
Part 3 (Extension of Part 2, Group 2): • CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors |
| Actual Study Start Date : | September 2, 2020 |
| Estimated Primary Completion Date : | April 2024 |
| Estimated Study Completion Date : | October 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Cholangiocarcinoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 1: Dose Escalation
Multiple doses of RLY-4008 for oral administration.
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Drug: RLY-4008
RLY-4008 is an oral inhibitor of FGFR2 |
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Experimental: Part 2: Dose Expansion
Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
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Drug: RLY-4008
RLY-4008 is an oral inhibitor of FGFR2 |
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Experimental: Part 3: Extension
Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
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Drug: RLY-4008
RLY-4008 is an oral inhibitor of FGFR2 |
Primary Outcome Measures :
- Objective Response Rate (ORR) assessed per RECIST v1.1 [ 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 ]
- Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-4008 [ Time Frame: 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 ]
- Number of patients with adverse events and serious adverse events [ Time Frame: Every cycle (4-week cycles) until study discontinuation, approximately 24 months ]
Secondary Outcome Measures :
- Duration of Response (DOR) assessed per RECIST v1.1 [ 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 ]
- FGFR2 gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue [ Time Frame: Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months ]
- Disease Control Rate (DCR) as assessed by RECIST v1.1 [ 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 ]
- Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
- Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
- Pharmacokinetic parameters including half-life (t1/2) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle though Cycle 4 (4-week cycles) ]
- Pharmacodynamic parameters including changes in fibroblast growth factor 23 (FGF-23) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
- Pharmacodynamic parameters including changes in carcinoembryonic antigen (CEA) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
- Pharmacodynamic parameters including changes in cancer antigen 19-9 (CA 19-9) [ Time Frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria
- Histologically or cytologically confirmed unresectable or metastatic solid tumor
- Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor
- Patient must have measurable disease per RECIST v1.1
- Patient has ECOG performance status of 0-1
- Patient must have disease that is refractory to standard therapy, disease that has not adequately responded to standard therapy, disease for which standard or curative therapy does not exist, or the patient must be intolerant to or have declined standard therapy
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Part 2 dose expansion patients with Cholangiocarcinoma:
- Group 1: CCA patients with an FGFR2 fusion previously treated with an FGFRi
- Group 2: CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
- Group 6: CCA patients with an FGFR2 fusion with no prior chemotherapy and not previously treated with an FGFRi. Prior adjuvant/neo-adjuvant treatment completed >6 months before enrollment is acceptable. A single cycle of palliative chemotherapy is allowed during screening
- Group 7: CCA patients with an FGFR2 mutation or amplification
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Part 2 dose expansion patients with other solid tumors (NOT Cholangiocarcinoma):
- Group 3: Non-CCA patients with an FGFR2 fusion
- Group 4: Non-CCA patients with an FGFR2 amplification
- Group 5: Non-CCA patients with an FGFR2 mutation
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Part 3 extension:
- CCA patients with an FGFR2 fusion with prior chemotherapy but not previously treated with an FGFRi
Key Exclusion Criteria
- Ongoing, clinically significant FGFRi-induced retinal detachment or an ongoing clinically significant corneal or retinal disorder
- Patient does not have adequate organ function (defined in protocol)
- Patient has active infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) (defined in protocol)
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04526106
Contacts
| Contact: Relay Therapeutics, Inc. | 339-230-7475 | ClinicalTrials@relaytx.com |
Locations
Show 46 study locations
Sponsors and Collaborators
Relay Therapeutics, Inc.
| Responsible Party: | Relay Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT04526106 |
| Other Study ID Numbers: |
RLY-4008-101 |
| First Posted: | August 25, 2020 Key Record Dates |
| Last Update Posted: | December 22, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Cholangiocarcinoma Neoplasms Adenocarcinoma |
Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type |