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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: LY3321367
* Drug: LY3300054


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3321367 Dose Escalation<br>LY3321367 given intravenously (IV). | Drug: LY3321367<br>* Administered IV<br>|
| Experimental: LY3321367 + LY3300054 Dose Escalation<br>LY3321367 and LY3300054 given IV. | Drug: LY3321367<br>* Administered IV<br>Drug: LY3300054<br>* Administered IV<br>|
| Experimental: LY3321367 Dose Expansion<br>LY3321367 given IV. | Drug: LY3321367<br>* Administered IV<br>|
| Experimental: LY3321367 + LY3300054 Dose Expansion<br>LY3321367 and LY3300054 given IV. | Drug: LY3321367<br>* Administered IV<br>Drug: LY3300054<br>* Administered IV<br>|
| Experimental: Japanese Arm D LY3321367<br>LY3321367 given IV. | Drug: LY3321367<br>* Administered IV<br>|
| Experimental: Japanese Arm E LY3300054<br>LY3300054 given IV. | Drug: LY3300054<br>* Administered IV<br>|
| Experimental: Japanese Arm F LY3321367 + LY3300054<br>LY3321367 and LY3300054 given IV. | Drug: LY3321367<br>* Administered IV<br>Drug: LY3300054<br>* Administered IV<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TIM-3, PD-L1