Print

Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts 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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation 		LOXO-435 administered orally to participants with FGFR3-altered advanced solid tumors.
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
Experimental
Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization 		LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma. (Cohort to be implemented as needed, based on Sponsor's discretion.)
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
Experimental
Phase 1b: Cohort B1 LOXO-435 Monotherapy Dose Expansion 		LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who were previously treated with an FGFR inhibitor.
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
Experimental
Phase 1b: Cohort B2 LOXO-435 Monotherapy Dose Expansion 		LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
Experimental
Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab 		LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV) to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
  • Drug: Pembrolizumab
    IV
    Other names:
    • KEYTRUDA®
Experimental
Phase 1b: Cohort C1 LOXO-435 Monotherapy Dose Expansion 		LOXO-435 administered orally to participants with advanced solid tumors who have not received a prior FGFR inhibitor.
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02144

More Details

Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
13176154559
clinical_inquiry_hub@lilly.com

Detailed Description

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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.