A Study of LY3434172, a PD-1 and PD-L1 Bispecific Antibody, in Advanced Cancer

Phase 1

Terminated

Conditions: Advanced Cancer

Interventions: Drug: LY3434172

Registration Number: NCT03936959

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study is to evaluate the safety and tolerability of the study drug LY3434172, a PD-1/PD-L1 bispecific antibody, in participants with advanced solid tumors.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Must have histological or cytological evidence of a diagnosis of cancer that is not amenable/resistant to approved standard-of-care therapy for the following solid tumors: Melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, gastric cancer, colorectal cancer, biliary tract cancer, anal cancer, nasopharyngeal cancer, esophageal cancer, SCLC, ovarian cancer, mesothelioma, pan-tumor MSIhi solid tumors, hepatocellular carcinoma, merkel cell cancer, cutaneous squamous cell carcinoma, endometrial cancer, breast cancer, cervical cancer, thyroid cancer, salivary cancer, and prostate cancer who have received at least one line of standard systemic therapy for their respective tumor type in the metastatic setting with progressive locally advanced or metastatic disease. Prior anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) allowed if they received another therapy immediately prior to this study or there has been a lapse of approximately ≥90 days from prior therapy.
Must be willing to undergo pretreatment and on-treatment core needle or excisional tumor biopsies.
Have at least one measurable lesion assessable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Have adequate organ function.
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
Have an estimated life expectancy of 12 weeks, in the judgment 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 moderate or severe cardiovascular disease.
Have active or suspected autoimmune disease (eg. autoimmune vasculitis, autoimmune myocarditis, among others).
Have serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including known infection with human immunodeficiency virus (HIV) unless they are well controlled on highly active antiretroviral therapy (HAART) therapy with no evidence of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections within the last 2 years, and CD4 T-cells count > 350 cells/µl , 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, exceeding 10 milligrams/day of prednisone or equivalent). Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted.
Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea.
Evidence of interstitial lung disease or noninfectious pneumonitis (active or treated by corticosteroid therapy).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
3 Milligram (mg) - 10 mg LY3434172	LY3434172	3 mg LY3434172 administered intravenously (IV) on Day 1 Cycle 1 of 28-day cycle. 10 mg LY3434172 administered IV on Day 15 Cycle 1 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation.
30 mg LY3434172	LY3434172	30 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation.
100 mg LY3434172	LY3434172	100 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities (DLTs)	Baseline through Cycle 1 (Up to 42 Day Cycle)	A DLT is defined as adverse event/s of grade 3 or higher that occurs during the DLT observation period, which is Cycle 1 of each dose escalation cohort, and is clinically significant and definitely, probably, or possibly related to LY3434172, in the opinion of the investigator.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172	PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; Cycle 1 Day 15 (C1D15): Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion	PK: Cmin of LY3434172
PK: Maximum Concentration (Cmax) of LY3434172	PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion	PK: Cmax of LY3434172
PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172	PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion	PK: AUC 0-tlast of LY3434172
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	Baseline through Measured Progressive Disease (Up to 8.4 Months)	ORR: Percentage of participants who have received any amount of study drug, have at least one postbaseline tumor image, and achieved a best overall response (BOR) of confirmed Complete Response (CR) is defined a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Duration of Response (DOR)	Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Up to 8.4 Months)	DOR is defined only for responders (participants with a confirmed CR or PR). It is measured from the date of first evidence of a confirmed CR or PR to the date of the first observed radiographically documented progressive disease (PD), or the date of death due to any cause, whichever is earlier. If a responder is not known to have died or have objective progression as of the data inclusion cutoff date, DoR will be censored at the date of the last complete objective progression-free disease assessment.
Time to Response (TTR)	Baseline to Date of CR or PR (Up to 8.4 Months)	TTR is defined as the time from the date of first study treatment until the first evidence of confirmed CR or PR.
Disease Control Rate (DCR): Percentage of Participants Who Exhibit Stable Disease (SD), CR or PR	Baseline through Measured Progressive Disease (Up to 8.4 Months)	Disease control rate is defined as the number of participants with SD, confirmed PR, or confirmed CR (CR+PR+SD) divided by the number of enrolled participants who have received any quantity of study treatment.

Trial Locations

Locations (5): Universitair Ziekenhuis Gent
🇧🇪
Gent, Belgium
Asan Medical Center
🇰🇷
Songpa-gu, Seoul, Korea, Republic of
Institut Claudius Regaud - IUCT Oncopole
🇫🇷
Toulouse cedex 9, France
St Vincent's Hospital
🇦🇺
Sydney, New South Wales, Australia
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States