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

NCT03099109

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 16526
  • SECONDARY ID: I9A-MC-JLDA
  • SECONDARY ID: 2016-003195-42
  • NCT ID: NCT03099109

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
LY3321367LY3321367 Dose Escalation
LY3300054LY3321367 + LY3300054 Dose Escalation

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
LY3321367 Dose EscalationExperimentalLY3321367 given intravenously (IV).
  • LY3321367
LY3321367 + LY3300054 Dose EscalationExperimentalLY3321367 and LY3300054 given IV.
  • LY3321367
  • LY3300054
LY3321367 Dose ExpansionExperimentalLY3321367 given IV.
  • LY3321367
LY3321367 + LY3300054 Dose ExpansionExperimentalLY3321367 and LY3300054 given IV.
  • LY3321367
  • LY3300054
Japanese Arm D LY3321367ExperimentalLY3321367 given IV.
  • LY3321367
Japanese Arm E LY3300054ExperimentalLY3300054 given IV.
  • LY3300054
Japanese Arm F LY3321367 + LY3300054ExperimentalLY3321367 and LY3300054 given IV.
  • LY3321367
  • LY3300054

Eligibility Criteria

        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 not have experienced a Grade ≥3 immune-related AE or an immune-related
                  neurologic or ocular AE, pneumonitis or cardiomyopathy of any grade while
                  receiving prior immunotherapy.

               -  Must not have required immunosuppressive agents, other than corticosteroids for
                  the management of an adverse event and not currently requite maintenance doses of
                  >10 milligrams (mg) prednisone (or equivalent) per day.

          -  Must have at least 1 measurable lesion assessable using standard techniques by
             Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with DLTs
Time Frame:Baseline through Cycle 1 (28 Day Cycle)
Safety Issue:
Description: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

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • TIM-3
  • PD-L1

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