A Study of LY3415244 in Participants With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT03752177
• Recruitment Status: Terminated
• First Posted: November 23, 2018
• Results First Posted: August 31, 2021
• Last Update Posted: October 22, 2021
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The goal of this study is to evaluate the safety of LY3415244, a PD-L1/TIM-3 bispecific antibody, administered as monotherapy to participants with advanced solid tumors.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: LY3415244	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1a/1b Study of LY3415244, a Bispecific Antibody in Patients With Advanced Solid Tumors
• Actual Study Start Date: November 22, 2018
• Actual Primary Completion Date: October 9, 2019
• Actual Study Completion Date: October 9, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: LY3415244 Dose Escalation; Participants received 3 milligrams (mg) LY3415244 (Cohort A1), 10 mg LY3415244 (Cohort A2), 30 mg LY3415244 (Cohort A3) and 70 mg LY3415244 (Cohort A4) as an intravenous (IV) infusion on day (D)1 and D15 of each 28-day cycle every 2 weeks (Q2W).	Drug: LY3415244; Administered IV
Experimental: LY3415244 Dose Expansion; Phase 1b dose expansion was planned but not initiated as dose escalation ended at cohort A4. Study did not achieve its primary objective of establishing a recommended phase 2 dose (RP2D) due to early termination of the study by Cohort A4.	Drug: LY3415244; Administered IV

Outcome Measures

Primary Outcome Measures :

1. Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs) [ Time Frame: Baseline through Cycle 1 (28 Day Cycle) ]
   A DLT was defined as an adverse event (AE) occurring during Cycle 1(28 days) that was considered at least possibly related to study drug, was considered dose-dependent, and fulfilled a criteria selected (using the National Cancer Institute Common Terminology Criteria for Adverse Events,version 4.0 [NCI-CTCAE v 4.0] [NCI 2009]):Grade 3 thrombocytopenia requiring platelet transfusion or grade 4 thrombocytopenia. Grade greater than or equal to (≥) 3 febrile neutropenia, anemia requiring a blood transfusion and any other Grade 4 hematologic toxicity that last >7 days. Grade ≥ 3 colitis or noninfectious pneumonitis, Grade ≥ 3 fatigue lasting >7 days, Grade ≥ 3 hypertension despite of maximal medical therapy. Grade 4 immune-related adverse event (irAE), liver transaminase elevation >8x upper limit of normal (ULN) or total bilirubin >3x ULN.

Secondary Outcome Measures :

1. Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244 [ Time Frame: Cycle 1 Day 1 (C1D1) and C1D15: pre-dose, 2 hours(h), 4h, 24h, 72h, 120h and 168h post-dose; C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1 and C6D15: pre-dose ]
   Cmin of LY3415244 was evaluated.
2. Phase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline through Measured Progressive Disease (Up To 24 Months) ]
   ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
3. Phase1b: Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months) ]
   Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.
4. Phase1b: Time to Response (TTR) [ Time Frame: Baseline to Date of CR or PR (Up To 24 Months) ]
   Data were not captured as study was terminated early and no participant were enrolled into Phase 1b expansion. Time to treatment response was defined as date of first dose of study drug to the date of confirmed complete response (CR) or partial response (PR) using Response evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
5. Phase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease [ Time Frame: Baseline through Measured Progressive Disease (Up To 24 Months) ]
   DCR is the percentage of participants with a best overall response of CR, PR or stable disease (SD) as defined by RECIST v1.1. CR is defined as disappearance of all target and non-target lesions and no appearance of new lesions.PR is defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions (taking as reference the baseline sum LD),no progression of non-target lesions, and no appearance of new lesions.SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.
6. Phase1b: Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months) ]
   Progression-free survival time was measured from treatment start until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Patients who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of treatment start if no post-baseline radiographic assessment is available.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• For Phase 1a/b, histologic or cytologic confirmation of advanced solid tumor.
• For Phase 1a/b, biopsy of tumor samples are required. Newly obtained core or excisional biopsy of a tumor lesion prior to study enrollment and undergo a biopsy procedure during the study.
• Phase 1a, prior anti-PD-1 or anti-PD-L1 therapy or other immunotherapy is allowed.

• Phase 1b, prior anti-PD-1 or anti-PD-L1 therapy is required where anti-PD-1 or anti-PD-L1 is standard of care in respective tumor types if the following criteria are met:

  • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
  • Must have completely recovered to baseline level prior to screening from any adverse events (AEs) that occurred from receiving prior immunotherapy
  • Must not have experienced a Grade ≥3 immune-related AE or immune related neurologic or ocular AE, pneumonitis or cardiomyopathy of any grade while receiving prior immunotherapy
  • Must not have required immunosuppressive agent, other than corticosteroids for the management of an adverse event and not currently require maintenance doses of >10 milligrams (mg) prednisone (or equivalent) per day
• Must have at least 1 measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• Have adequate organ function.
• Have an estimated life expectancy ≥12 weeks, in the judgement of the investigator.

Exclusion Criteria:

• Have symptomatic central nervous system (CNS) malignancy or metastasis not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and their disease is asymptomatic and radiographically stable for at least 30 days.
• 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 known 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.

Contacts and Locations

Locations

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Belgium

Institut Jules Bordet

Brussel, Belgium, 1000

Universitair Ziekenhuis Gent

Gent, Belgium, 9000

Japan

National Cancer Center Hospital East

Kashiwa, Chiba, Japan, 277 8577

National Cancer Center Hospital

Chuo-Ku, Tokyo, Japan, 104-0045

Sponsors and Collaborators

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

  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:

Study Protocol  [PDF] December 13, 2018

Statistical Analysis Plan  [PDF] October 24, 2018

More Information

Additional Information:

A Study of LY3415244 in Participants With Advanced Solid Tumors 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03752177
• Other Study ID Numbers: 17099; J1C-MC-JZDA ( Other Identifier: Eli Lilly and Company ); 2018-001598-25 ( EudraCT Number )
• First Posted: November 23, 2018
• Results First Posted: August 31, 2021
• Last Update Posted: October 22, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eli Lilly and Company:

TIM-3; PD-L1

Additional relevant MeSH terms:

Neoplasms