FORAGER-1: A Study of LOXO-435 (LY3866288) 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 by itself or when it is combined with other standard medicines that treat cancer. 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 Sex
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: Presence of an alteration in FGFR3 or its ligands - Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration - Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic - Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration - Measurability of disease: - Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1) - Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1 - Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5 - Less than or equal to 2 for Cohorts B1, B2, B4, and C1 - 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, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting - There is no restriction on number of prior therapies - Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC - FGFR inhibitor specific requirements: - Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required - Cohort B1/B4: Participants must have been previously treated with erdafitinib - Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve

Exclusion Criteria

  • Participants with primary central nervous system (CNS) malignancy - Untreated or uncontrolled CNS metastases - Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible - 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)
Masking Description
Cohort A2 is randomized

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation 		LOXO-435 administered orally
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
Experimental
Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization 		LOXO-435 administered orally
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
Experimental
Phase 1b: Cohort B1, B2, B4, and C1 LOXO-435 Monotherapy Dose Expansion 		LOXO-435 administered orally
  • 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)
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
  • Drug: Pembrolizumab
    IV
Experimental
Phase 1b: Cohort B5 LOXO-435 Plus Pembrolizumab Plus Enfortumab Vedotin 		LOXO-435 administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV
  • Drug: LOXO-435
    Oral
    Other names:
    • LY3866288
  • Drug: Pembrolizumab
    IV
  • Drug: enfortumab vedotin
    IV

Recruiting Locations

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114

More Details

Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
LillyTrials@Lilly.com

Detailed Description

This is an open-label, multi-center, phase 1 study in participants with FGFR3-altered advanced solid tumor malignancy including metastatic urothelial cancer (UC). The study will be conducted in 2 phases: Phase 1a dose escalation (Cohort A1) and dose optimization (Cohort A2) and Phase 1b dose expansion. Phase 1a will assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the optimal dose for further expansion. Phase 1b will include 6 dose expansion cohorts to evaluate the efficacy and safety of LOXO-435 as monotherapy or in combinations with pembrolizumab with or without enfortumab vedotin.