E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic cholangiocarcinoma (CCA), other advanced solid tumors with an FGFR2-alteration or other potential FGFR2-dependent tumors |
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E.1.1.1 | Medical condition in easily understood language |
Cholangiocarcinoma (CCA) and Other Advanced Solid Tumors |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 27.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073077 |
E.1.2 | Term | Intrahepatic cholangiocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 27.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008595 |
E.1.2 | Term | Cholangiocarcinoma NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014735 |
E.1.2 | Term | Endometrial cancer NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017760 |
E.1.2 | Term | Gastric cancer NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006192 |
E.1.2 | Term | Breast cancer NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1 • To determine the MTD and RP2D of RLY-4008 • To determine the safety and tolerability of RLY-4008 • To evaluate the efficacy of RLY-4008 by objective response rate (ORR) assessed by Independent Review Committee (IRC) Part 4 • To assess the safety and tolerability of RLY-4008.
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E.2.2 | Secondary objectives of the trial |
Part 1 • To evaluate FGFR2 status in blood and tumor tissue by next generation nucleic acid sequencing • To define the PK profile of RLY-4008 and its metabolites if appropriate • To assess the pharmacodynamics of RLY-4008 by monitoring blood markers (eg. CA 19-9, CEA, FGF23) • To characterize the preliminary anti-tumor activity of RLY-4008 per RECIST 1.1 Part 2 and 3 • To determine the duration of response (DOR) by IRC
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria for the study, including specific criteria for Part 1, 2 and 3 can be found in the study protocol (section 5.2).
Part 4 14. Patient is currently receiving RLY-4008 on RLY-4008-101 Study and benefiting from treatment as assessed by the investigator. |
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E.4 | Principal exclusion criteria |
Main exclusion criteria for the study, including specific criteria for Part 1, 2 and 3 can be found in the study protocol (section 5.3).
Part 4 21. Patient has permanently discontinued treatment with RLY-4008 for any reason before enrolling into Part 4. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• MTD and RP2D • Overall safety profile of RLY-4008 as assessed by the type, frequency, severity, timing and relationship to RLY-4008 of any adverse events (AEs), serious AEs (SAEs), changes in vital signs, electrocardiograms (ECGs) and safety laboratory tests. All AEs and SAEs will be collected and graded to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. • To evaluate the efficacy of RLY-4008 by objective response rate (ORR) assessed by Independent Review Committee (IRC) using RECIST v.1.1
Part 4 • To assess the safety and tolerability of RLY-4008 • Frequency, severity, timing, and relationship to RLY-4008 of any AEs and SAEs. All AEs and SAEs will be collected and graded according to NCI CTCAE, Version 5.0. • Dose modification (e.g., dose interruption, dose reduction, dose discontinuation)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The minimum duration of participation for a patient is approximately 3 months including a Screening Period up to 28 days, a Treatment Period of up to 1 cycle (28 days), an End of Treatment visit within 14 days of the last dose of RLY-4008, and a Safety Follow-up to document any new AE or resolution of any residual AE, 30 days (±7 days) after the last dose of RLY-4008, or prior to the initiation of a new antineoplastic therapy. All AEs should be followed until they are resolved, or the Investigator assesses them as chronic or stable, the patient’s participation in the study ends, or until a subsequent antineoplastic therapy is initiated. |
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E.5.2 | Secondary end point(s) |
• FGFR2 genotype in blood and tumor tissue • PK parameters of RLY-4008 (and its metabolites if appropriate) including, but not limited to Maximum Concentration (Cmax), Time to Maximum Concentration (Tmax), Area Under the Concentration-Time Curve (AUC), effective half-life(T1/2eff), clearance (CL/F), and other relevant parameters • Pharmacodynamic parameters: including, but not limited to blood markers (eg. CA 19-9, CEA, FGF23) • Overall response rate (ORR), Duration of Response (DOR), and Disease Control Rate (DCR) per RECIST 1.1 • To determine the duration of response (DOR) by Independent Review Committee (IRC) using RECIST v.1.1
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Plasma samples for extensive PK will be collected on Cycle 1 Day 1 (through 24 hours post dose) and Cycle 1 Day 15 (through 8 hours post dose). On Day 1 of Cycles 2, 3, and 4, samples will only be collected pre-dose (within 30 minutes pre-dose). ORR is defined as the proportion of patients achieving Complete response (CR) and partial response (PR). Confirmed responses are those that persist on repeat tumor assessments for at least 4 weeks after initial documentation or response. Otherwise, the patient will be counted as a non-responder in the assessment of ORR. DOR is defined as the time from first documentation of CR or PR until the time of first documentation of progressive disease (PD) or death due to any cause.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To define the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) and evaluate the efficacy, safety, and tolerability of RLY4008
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Singapore |
Hong Kong |
Taiwan |
Australia |
Korea, Republic of |
United Kingdom |
United States |
France |
Germany |
Netherlands |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the last visit of the last patient for any protocol-related activity. For individual patients, study completion is defined as the time of the patient’s last data collection. A patient is considered to have completed the study if he/she has discontinued the study for any of the following reasons: withdrawal of consent by the patient, contact has been adequately attempted, but patients are considered lost to follow-up, death, sponsor decision |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |