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A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.
5 years) and possibly longer if the disease does not get worse.
Study details:
This is an open-label, multi-center, phase 1a/b study in participants with FGFR3-altered advanced solid tumors, including metastatic urothelial cancer (UC). The study will be conducted in 2 phases: Dose escalation and dose optimization (1a) and dose expansion (1b). Phase 1a will include up to 2 cohorts to assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D) (or optimal dose).
Phase 1b will include 4 dose expansion cohorts of participants with prespecified activating FGFR3 alterations to evaluate the efficacy and safety of LOXO-435 at the RP2D. Cohort B will enroll pts with metastatic UC and includes three cohorts to evaluate LOXO-435 as monotherapy (B1, B2) and in combination with pembrolizumab (B3). Cohort C will enroll pts with non-UC advanced solid tumors and includes a cohort to evaluate LOXO-435 as monotherapy (C1).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-01-12
Primary completion: 2025-06-01
Study completion finish: 2025-06-01
Study type
TREATMENT
Phase
PHASE1
Trial ID
NCT05614739
Intervention or treatment
DRUG: LOXO-435
DRUG: Pembrolizumab
Conditions
- • Urinary Bladder Neoplasms
- • Neoplasm Metastasis
- • Ureteral Neoplasms
Find a site
Closest Location:
Royal North Shore Hospital
Research sites nearby
Select from list below to view details:
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
Kinghorn Cancer Centre
Darlinghurst, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation
| DRUG: LOXO-435
|
EXPERIMENTAL: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization
| DRUG: LOXO-435
|
EXPERIMENTAL: Phase 1b: Cohort B1 LOXO-435 Monotherapy Dose Expansion
| DRUG: LOXO-435
|
EXPERIMENTAL: Phase 1b: Cohort B2 LOXO-435 Monotherapy Dose Expansion
| DRUG: LOXO-435
|
EXPERIMENTAL: Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab
| DRUG: LOXO-435
|
EXPERIMENTAL: Phase 1b: Cohort C1 LOXO-435 Monotherapy Dose Expansion
| DRUG: LOXO-435
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Phase 1a: To determine the recommended phase 2 dose (RP2D)/optimal dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs) | Number of participants with DLTs | Minimum of the first 21-day cycle of LOXO-435 treatment |
Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR) | ORR per investigator assessed RECIST v1.1 | Up to approximately 30 months or 2.5 years |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC) | PK of LOXO-435: AUC | Up to 2 months |
To assess the PK of LOXO-435: Minimum plasma concentration (Cmin) | PK of LOXO-435: Cmin | Up to 2 months |
To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR) | DOR per investigator assessed RECIST 1.1 | Up to approximately 30 months or 2.5 years |
To evaluate the preliminary antitumor activity of LOXO-435: Time to response (TTR) | TTR | Up to approximately 30 months or 2.5 years |
To evaluate the preliminary antitumor activity of LOXO-435: Progression-free survival (PFS) | PFS per investigator assessed RECIST 1.1 | Up to approximately 30 months or 2.5 years |
To evaluate the preliminary antitumor activity of LOXO-435: Disease control rate (DCR) | DCR per investigator assessed RECIST 1.1 | Up to approximately 30 months or 2.5 years |
To evaluate the preliminary antitumor activity of LOXO-435: Overall survival (OS) | OS | Up to approximately 30 months or 2.5 years |
Change from baseline in bladder-related symptoms, measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) subscale (BlCS) | The BlCS has 12 items with a total score range of 0 to 48, with higher scores representing better bladder-related symptoms. A ≥ 4-point score change from baseline will be considered as clinically meaningful improvement in bladder-related symptoms | Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 day cycles) |
Change from baseline in physical function, measured by FACT- Physical Well-being Scale (PWB) subscale | The PWB subscale has 7 items with a total score range of 0-28, with higher scores representing better physical function. A ≥ 3-point score change from baseline for a participant will be considered as clinically meaningful improvement in physical function. | Up to approximately 30 months or 2.5 years |
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