A Study of LY3321367 Alone or With LY3300054 in Participants With Advanced Relapsed/Refractory Solid Tumors

A Phase 1a/1b Study of LY3321367, an Anti-TIM-3 Antibody, Administered Alone or in Combination With LY3300054, an Anti-PD-L1 Antibody, in Advanced Relapsed/Refractory Solid Tumors

The purpose of this study is to evaluate the safety of the study drug known as LY3321367, an anti-T-cell immunoglobulin and mucin-domain domain-containing molecule-3 (TIM-3) antibody administered alone or in combination with LY3300054, an anti-programmed death ligand 1 (PD-L1) antibody, in participants with advanced relapsed/refractory solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: LY3321367; Drug: LY3300054

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System
• Spain
  • Madrid, Spain, 28050
    • Hospital Madrid Norte Sanchinarro
  • Madrid, Spain, 28040
    • Fundación Jiménez Díaz-Oncology
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Hospital Clinico Universitario Virgen de la Victoria
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • The University of Arizona Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Columbia University College of Phys & Surgeons
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Peggy and Charles Stephenson Oklahoma Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute SCRI
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • The START Center for Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For Ph1a monotherapy and combination cohorts, histologic or cytologic confirmation of advanced solid tumor.

• For Phase 1a and 1b, prior PD-1 or PD-L1 therapy or other immunotherapy is allowed, if the following criteria are met:

  • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
  • Must have completely recovered or recovered to baseline prior to screening from any prior AEs occurring while receiving prior immunotherapy.

• Must have provided tumor tissue sample, as follows:

  • For participants entering Ph1a: have submitted, if available, an archival tumor tissue sample.
  • For participants entering Ph1b: have submitted, a sample from a newly obtained core or excisional biopsy of a tumor lesion or a recent biopsy defined by 6 months of study enrollment (Ph1b).
• Must have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Must have adequate organ function.
• Have an estimated life expectancy of 12 weeks, in judgement of the investigator.

Exclusion Criteria:

• Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids (participants receiving anticonvulsants are eligible).
• Have received a live vaccine within 30 days before the first dose of study treatment.
• If female, is pregnant, breastfeeding, or planning to become pregnant.
• Have a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the participant's participation.
• Have moderate or severe cardiovascular disease.
• Have a serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including active or chronic infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment.
• Use of escalating or chronic supraphysiologic doses of corticosteroids or immunosuppressive agents (such as, cyclosporine). [Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted].
• Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
• Evidence of interstitial lung disease or noninfectious pneumonitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3321367 Dose Escalation; LY3321367 given intravenously (IV).	Drug: LY3321367; Administered IV
Experimental: LY3321367 + LY3300054 Dose Escalation; LY3321367 and LY3300054 given IV.	Drug: LY3321367; Administered IV; Drug: LY3300054; Administered IV
Experimental: LY3321367 Dose Expansion; LY3321367 given IV.	Drug: LY3321367; Administered IV
Experimental: LY3321367 + LY3300054 Dose Expansion; LY3321367 and LY3300054 given IV.	Drug: LY3321367; Administered IV; Drug: LY3300054; Administered IV
Experimental: Japanese Arm D LY3321367; LY3321367 given IV.	Drug: LY3321367; Administered IV
Experimental: Japanese Arm E LY3300054; LY3300054 given IV.	Drug: LY3300054; Administered IV
Experimental: Japanese Arm F LY3321367 + LY3300054; LY3321367 and LY3300054 given IV.	Drug: LY3321367; Administered IV; Drug: LY3300054; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with DLTs	Dose Limiting Toxicity (DLT) is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.	Baseline through Cycle 1 (28 Day Cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Cmax of LY3321367	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3321367	Cycle 1 Day 1 through Follow-Up (Estimated up to 6 Months)
PK: Cmax of LY3321367 in Combination with LY3300054	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3321367 in Combination with LY3300054	Cycle 1 Day 1 through Follow-Up (Estimated up to 6 Months)
ORR: Percentage of Participants With a CR or PR	Objective Response Rate (ORR) is the percentage of participants with confirmed best overall tumor response of Complete Response (CR) or Partial Response (PR).	Baseline to Measured Progressive Disease (Estimated up to 6 Months)
PFS	Progression Free Survival (PFS) is defined as the date of the first dose to the first date of objectively determined progressive disease or death from any cause, whichever is earlier.	Baseline to Objective Progression or Death Due to Any Cause (Estimated Up to 12 Months)
DoR	Duration of Response (DoR) is defined as the time from the date of the first CR or PR to the first date of progressive disease (PD) or death from any cause.	Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)
TTR	Time to Response (TTR) is defined as time from treatment start to first documentation of response.	Baseline to Date of CR or PR (Estimated up to 6 Months)
DCR: Percentage of Participants who Exhibit SD, CR or PR	Disease Control Rate (DCR) is the percentage of participants with stable disease (SD), confirmed PR or confirmed CR (CR+PR+SD).	Baseline through Measured Progressive Disease (Estimated up to 6 Months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM- 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Harding JJ, Moreno V, Bang YJ, Hong MH, Patnaik A, Trigo J, Szpurka AM, Yamamoto N, Doi T, Fu S, Calderon B, Velez de Mendizabal N, Calvo E, Yu D, Gandhi L, Liu ZT, Galvao VR, Leow CC, de Miguel MJ. Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody. Clin Cancer Res. 2021 Apr 15;27(8):2168-2178. doi: 10.1158/1078-0432.CCR-20-4405. Epub 2021 Jan 29.

Helpful Links

• A Study of LY3321367 Alone or With LY3300054 in Participants With Advanced Relapsed/Refractory Solid Tumors

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2017
• Primary Completion (Actual): December 10, 2019
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: March 29, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: PD-L1; TIM-3
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 16526; I9A-MC-JLDA (Other Identifier: Eli Lilly and Company); 2016-003195-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No