A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors

Pancreatic Cancer Clinical Trial

— PACT  

Official title:

A Phase 1a/1b Study of a Novel Anti-PD-L1 Checkpoint Antibody (LY3300054) Administered Alone or in Combination With Other Agents in Advanced Refractory Solid Tumors (Phase 1a/1b Anti-PD-L1 Combinations in Tumors-PACT)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02791334
• Other study ID #: 16088
• Secondary ID: I8J-MC-JYCA2016-
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 29, 2016
• Est. completion date: July 2024

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the safety and tolerability of anti-programmed cell death ligand 1 (PD-L1) checkpoint antibody LY3300054 in participants with advanced refractory solid tumors.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 215
• Est. completion date: July 2024
• Est. primary completion date: May 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic or cytologic confirmation of advanced solid tumor.

• For LY3300054 + abemaciclib only: No participants with liver metastases. Participants must have normal aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin.

• For LY3300054 + abemaciclib in HR+, HER- breast cancer:

• Express at least 1 of the hormone receptors [HR; estrogen receptor (ER) or progesterone receptor (PR)] by immunohistochemistry (IHC) to fulfill the requirement for HR+ disease on the primary tumor or metastatic lesion of the breast cancer. ER and PR assays are considered positive if there is at least 1% positive tumor nuclei in their sample as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) or local guidelines.

• To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP or local guidelines.

• Most recent HR and HER2 receptor testing should be used to determine eligibility.

• Have previously received prior treatment with at least 1 but no more than 3 chemotherapy regimens in the metastatic setting.

• Have AST, ALT, GGT, and AP that are =2.5x upper limit of normal (ULN) and normal bilirubin (total and direct) regardless of liver involvement.

• For LY3300054 + merestinib in pancreatic cancer:

• Histologically or cytological confirmed diagnosis of metastatic or locally advanced, unresectable pancreatic adenocarcinoma (excluding other pancreatic malignancies for example, acinar cell carcinomas, adenosquamous carcinomas, and neuroendocrine islet cell neoplasms).

• Have had disease progression, be refractory or intolerant to no more than 2 prior systemic regimens.

• For LY3300054 + LY3321367 in PD-1/PD-L1-naive, MSI-H/MMR-deficient advanced solid tumors:

• Have histologically or cytologically confirmed diagnosis of advanced solid tumor AND shown to be MSI-H or MMR-deficient.

• For LY3300054 + LY3321367 in PD-1/PD-L1- resistant/refractory, MSI-H/MMR-deficient advanced solid tumors:

• Have histologically or cytologically confirmed diagnosis of advanced solid tumor AND shown to be MSI-H or MMR-deficient.

• Prior exposure to PD-1/PD-L1 agent regardless of response.

• For Phase 1b LY3300054 monotherapy or combination therapy, no prior treatment with a PD-1 or PD-L1 agent is allowed.

• Exception: the LY3321367 combination in participants with PD-1/PD-L1- resistant/refractory, MSI-H, where prior exposure to PD-1/PD-L1 agent required.

• For Phase 1a LY3300054 monotherapy or combination therapy, previous immunotherapy is acceptable 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 adverse events (AEs) occurring while receiving prior immunotherapy.

• Must not have experienced a Grade =3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy.

• Must not have required the use of additional immunosuppressive agents other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of >10 milligrams prednisone or equivalent per day.

• Have at least 1 measurable lesion assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

• 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.

• Have submitted a tumor tissue sample, as follows:

• For participants entering the Phase 1a dose escalation: have submitted, if available, the most recent archival tumor tissue sample.

• For those participating ONLY in Phase 1b expansions: Have submitted tumor tissue sample from a newly obtained core or excisional biopsy for a tumor lesion (preferred) or a recent biopsy taken with 3 months prior to study enrollment and following the participants most recent prior systemic treatment and be willing to undergo a biopsy procedure during the study treatment period for collection of additional tumor tissue sample.

Exclusion Criteria:

• Have a serious concomitant systemic disorder including human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorder or disease requiring high dose of steroids.

• Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection or chronic diarrhea.

• Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.

• Have an active infection requiring systemic therapy.

• Have moderate or severe cardiovascular disease.

• Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment.

• Have received a live vaccine within 30 days before the first dose of study treatment.

• Have a significant bleeding disorder or vasculitis or had a Grade =3 bleeding episode within 12 weeks prior to enrollment.

Related Conditions & MeSH terms

• Breast Cancer (HR+HER2-)
• Cutaneous Melanoma
• Microsatellite Instability
• Microsatellite Instability-High (MSI-H) Solid Tumors
• Neoplasms
• Pancreatic Cancer
• Solid Tumor

Intervention

Drug:
• LY3300054
Administered IV
• Ramucirumab
Administered IV
• Abemaciclib
Administered orally
• Merestinib
Administered orally
• LY3321367
Administered IV

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Canada	Princess Margaret Hospital	Toronto	Ontario
France	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux
France	Gustave Roussy	Villejuif Cedex
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Spain	Hospital Madrid Norte Sanchinarro	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	The START Center for Cancer Care	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs)		Baseline through Cycle 1 (Approximately 28 Days)
Secondary	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3300054		Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Secondary	PK: Cmax of Ramucirumab		Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Secondary	PK: Cmax of Abemaciclib		Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Secondary	PK: Cmax of Merestinib		Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Secondary	PK: Cmax of LY3321367		Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Secondary	Objective Response Rate (ORR): Proportion of Participants With a Complete Response (CR) or Partial Response (PR)		Baseline to Measured Progressive Disease (Approximately 6 Months )
Secondary	Progression Free Survival (PFS)		Baseline to Measured Progressive Disease or Death (Approximately 12 Months)
Secondary	Duration of Response (DoR)		Date of CR or PR to Date of Measured Progressive Disease or Death Due to Any Cause (Approximately 12 Months)
Secondary	Time to Response (TTR)		Baseline to Date of CR or PR (Approximately 6 Months)
Secondary	Disease Control Rate (DCR): Proportion of Participants who Exhibit Stable Disease (SD), CR or PR		Baseline to Measured Progressive Disease (Approximately 6 Months)

External Links

•   A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors