A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3

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

  • Urinary Bladder Neoplasms
  • Neoplasm Metastasis
  • Ureteral Neoplasms

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).