Clinical trial NCT03099109: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: TIM-3
PD-L1
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2017-04-04
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: Number of Participants with DLTs
timeFrame: Baseline through Cycle 1 (28 Day Cycle)
Secondary outcomes:
measure: PK: Cmax of LY3321367
timeFrame: Cycle 1 Day 1 through Follow-Up (Estimated up to 6 Months)
measure: PK: Cmax of LY3321367 in Combination with LY3300054
timeFrame: Cycle 1 Day 1 through Follow-Up (Estimated up to 6 Months)
measure: ORR: Percentage of Participants With a CR or PR
timeFrame: Baseline to Measured Progressive Disease (Estimated up to 6 Months)
measure: PFS
timeFrame: Baseline to Objective Progression or Death Due to Any Cause (Estimated Up to 12 Months)
measure: DoR
timeFrame: Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)
measure: TTR
timeFrame: Baseline to Date of CR or PR (Estimated up to 6 Months)
measure: DCR: Percentage of Participants who Exhibit SD, CR or PR
timeFrame: Baseline through Measured Progressive Disease (Estimated up to 6 Months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Columbia University College of Phys & Surgeons
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: Peggy and Charles Stephenson Oklahoma Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute SCRI
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: The START Center for Cancer Care
state: Texas
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
state: Andalucia
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz-Oncology
city: Madrid
country: Spain
facility: Hospital Madrid Norte Sanchinarro
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:
citation: Harding JJ, Moreno V, Bang YJ, Hong MH, Patnaik A, Trigo J, Szpurka AM, Yamamoto N, Doi T, Fu S, Calderon B, Velez de Mendizabal N, Calvo E, Yu D, Gandhi L, Liu ZT, Galvao VR, Leow CC, de Miguel MJ. Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody. Clin Cancer Res. 2021 Apr 15;27(8):2168-2178. doi: 10.1158/1078-0432.CCR-20-4405. Epub 2021 Jan 29.