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

Phase 1
Completed
Conditions
Solid Tumor
Interventions
Drug: LY3321367
Drug: LY3300054
Registration Number
NCT03099109
Lead Sponsor
Eli Lilly and Company
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
209
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.

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
LY3321367 + LY3300054 Dose ExpansionLY3321367LY3321367 and LY3300054 given IV.
Japanese Arm F LY3321367 + LY3300054LY3300054LY3321367 and LY3300054 given IV.
LY3321367 Dose EscalationLY3321367LY3321367 given intravenously (IV).
LY3321367 Dose ExpansionLY3321367LY3321367 given IV.
LY3321367 + LY3300054 Dose ExpansionLY3300054LY3321367 and LY3300054 given IV.
Japanese Arm E LY3300054LY3300054LY3300054 given IV.
LY3321367 + LY3300054 Dose EscalationLY3321367LY3321367 and LY3300054 given IV.
LY3321367 + LY3300054 Dose EscalationLY3300054LY3321367 and LY3300054 given IV.
Japanese Arm F LY3321367 + LY3300054LY3321367LY3321367 and LY3300054 given IV.
Japanese Arm D LY3321367LY3321367LY3321367 given IV.
Primary Outcome Measures
NameTimeMethod
Number of Participants with DLTsBaseline through Cycle 1 (28 Day Cycle)

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.

Secondary Outcome Measures
NameTimeMethod
TTRBaseline to Date of CR or PR (Estimated up to 6 Months)

Time to Response (TTR) is defined as time from treatment start to first documentation of response.

PK: Cmax of LY3321367Cycle 1 Day 1 through Follow-Up (Estimated up to 6 Months)

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3321367

PK: Cmax of LY3321367 in Combination with LY3300054Cycle 1 Day 1 through Follow-Up (Estimated up to 6 Months)

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3321367 in Combination with LY3300054

ORR: Percentage of Participants With a CR or PRBaseline to Measured Progressive Disease (Estimated up to 6 Months)

Objective Response Rate (ORR) is the percentage of participants with confirmed best overall tumor response of Complete Response (CR) or Partial Response (PR).

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

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.

DCR: Percentage of Participants who Exhibit SD, CR or PRBaseline through Measured Progressive Disease (Estimated up to 6 Months)

Disease Control Rate (DCR) is the percentage of participants with stable disease (SD), confirmed PR or confirmed CR (CR+PR+SD).

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

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.

Trial Locations

Locations (15)

Fundación Jiménez Díaz-Oncology

🇪🇸

Madrid, Spain

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Severance Hospital Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Hospital Madrid Norte Sanchinarro

🇪🇸

Madrid, Spain

Hospital Clinico Universitario Virgen de la Victoria

🇪🇸

Malaga, Andalucia, Spain

Columbia University College of Phys & Surgeons

🇺🇸

New York, New York, United States

Peggy and Charles Stephenson Oklahoma Cancer Center

🇺🇸

Oklahoma City, Oklahoma, United States

The START Center for Cancer Care

🇺🇸

San Antonio, Texas, United States

The University of Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

National Cancer Center Hospital

🇯🇵

Chuo-Ku, Tokyo, Japan

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

National Cancer Center Hospital East

🇯🇵

Kashiwa, Chiba, Japan

Sarah Cannon Research Institute SCRI

🇺🇸

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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