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

NCT03099109 | Completed Phase 1 FDA Drug

• 3 other identifiers: 16526I9A-MC-JLDA2016-003195-42
• Study Type: interventional
• Target: 209
• Locations: 4 countries
• Sites: 15

Brief Summary

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.

Conditions

Solid Tumor

Keywords

TIM-3; PD-L1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• PK: Cmax of LY3321367

  Cycle 1 Day 1 through Follow-Up (Estimated up to 6 Months)

• PK: 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

  Baseline to Measured Progressive Disease (Estimated up to 6 Months)

• PFS

  Baseline to Objective Progression or Death Due to Any Cause (Estimated Up to 12 Months)

• DoR

  Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)

Study Arms (7)

LY3321367 Dose Escalation

EXPERIMENTAL

LY3321367 given intravenously (IV).

Drug: LY3321367

LY3321367 + LY3300054 Dose Escalation

EXPERIMENTAL

LY3321367 and LY3300054 given IV.

Drug: LY3321367; Drug: LY3300054

LY3321367 Dose Expansion

EXPERIMENTAL

LY3321367 given IV.

Drug: LY3321367

LY3321367 + LY3300054 Dose Expansion

EXPERIMENTAL

LY3321367 and LY3300054 given IV.

Drug: LY3321367; Drug: LY3300054

Japanese Arm D LY3321367

EXPERIMENTAL

LY3321367 given IV.

Drug: LY3321367

Japanese Arm E LY3300054

EXPERIMENTAL

LY3300054 given IV.

Drug: LY3300054

Japanese Arm F LY3321367 + LY3300054

EXPERIMENTAL

LY3321367 and LY3300054 given IV.

Drug: LY3321367; Drug: LY3300054

Interventions

LY3321367 DRUG

Administered IV

Japanese Arm D LY3321367; Japanese Arm F LY3321367 + LY3300054; LY3321367 + LY3300054 Dose Escalation; LY3321367 + LY3300054 Dose Expansion; LY3321367 Dose Escalation; LY3321367 Dose Expansion

LY3300054 DRUG

Administered IV

Japanese Arm E LY3300054; Japanese Arm F LY3321367 + LY3300054; LY3321367 + LY3300054 Dose Escalation; LY3321367 + LY3300054 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (15)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University College of Phys & Surgeons

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Peggy and Charles Stephenson Oklahoma Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277 8577, Japan

Location

National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

Location

Fundación Jiménez Díaz-Oncology

Madrid, 28040, Spain

Location

Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain

Location

Related Publications (1)

• 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.

  PMID: 33514524 DERIVED

Related Links

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

MeSH Terms

Interventions

LY3321367; LY3300054

Study Officials

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 4, 2017
• Study Start: April 12, 2017
• Primary Completion: December 10, 2019
• Study Completion: August 30, 2023
• Last Updated: October 17, 2023

Record last verified: 2023-10

Locations

US (8); ES (3); JP (2); KR (2)