Clinical trial NCT03752177: A Study of LY3415244 in Participants With Advanced Solid Tumors
Official title: A Phase 1a/1b Study of LY3415244, a Bispecific Antibody in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: TIM-3
PD-L1
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-11-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)
timeFrame: Baseline through Cycle 1 (28 Day Cycle)
Secondary outcomes:
measure: Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244
timeFrame: 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
measure: Phase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline through Measured Progressive Disease (Up To 24 Months)
measure: Phase1b: Duration of Response (DoR)
timeFrame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)
measure: Phase1b: Time to Response (TTR)
timeFrame: Baseline to Date of CR or PR (Up To 24 Months)
measure: Phase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease
timeFrame: Baseline through Measured Progressive Disease (Up To 24 Months)
measure: Phase1b: Progression Free Survival (PFS)
timeFrame: Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: