CLINICAL TRIAL / NCT05614739
A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
- Interventional
- Recruiting
- NCT05614739
Contact Information
An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations
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.
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).
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor
or blood sample that is deemed as actionable.
- Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
- Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC)
that is locally advanced or metastatic with a qualifying FGFR3 alteration.
- Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial
cancer that is locally advanced or metastatic with a prespecified activating
FGFR3 alteration.
- Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial
solid tumor malignancy that is locally advanced or metastatic with a prespecified
activating FGFR3 alteration.
- Measurability of disease:
- Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation
Criteria in Solid Tumors v 1.1 (RECIST v1.1)
- Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST
v1.1
- Have adequate archival tumor tissue sample available or undergo a screening biopsy if
allowed per country-specific regulations.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Prior Systemic Therapy Criteria:
- Cohort A1/C1: Participant has received all standard therapies for which the
participant was deemed to be an appropriate candidate by the treating
Investigator; OR the participant is refusing the remaining most appropriate
standard of care treatment; OR there is no standard therapy available for the
disease. There is no restriction on number of prior therapies.
- Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen in
the advanced or metastatic setting. There is no restriction on number of prior
therapies.
- FGFR inhibitor specific requirements:
- Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
- Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
- Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
- Participants with primary central nervous system (CNS) malignancy.
- Known or suspected history of uncontrolled CNS metastases.
- Current evidence of corneal keratopathy or retinal disorder.
- Have a history and/or current evidence of extensive tissue calcification.
- Any serious unresolved toxicities from prior therapy.
- Significant cardiovascular disease.
- Prolongation of the QT interval corrected for heart rate using Fridericia's formula
(QTcF).
- Active uncontrolled systemic infection or other clinically significant medical
conditions.
- Participants who are pregnant, lactating, or plan to breastfeed during the study or
within 6 months of the last dose of study treatment. Participants who have stopped
breastfeeding may be enrolled.