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

NCT ID: NCT02791334

Last Updated: 2024-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-29
• Study Completion Date: 2024-06-27

Brief 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LY3300054

LY3300054 given intravenously (IV) on day 1 and day 15 of a 28 day cycle or LY3300054 given IV on day 1 of a 21 (or 28) day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

LY3300054 + Ramucirumab

LY3300054 and ramucirumab given IV on day 1 and day 15 of a 28 day cycle or ramucirumab given IV on day 1 and day 8 and LY3300054 given IV on day 1 of a 21 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

Ramucirumab

Intervention Type: DRUG

Administered IV

Abemaciclib + LY3300054

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

Abemaciclib

Intervention Type: DRUG

Administered orally

LY3300054 + Abemaciclib (Concurrent Dosing)

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

Abemaciclib

Intervention Type: DRUG

Administered orally

LY3300054 + Abemaciclib

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle. This arm will only be initiated if required.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

Abemaciclib

Intervention Type: DRUG

Administered orally

LY3300054 + Merestinib

LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

Merestinib

Intervention Type: DRUG

Administered orally

LY3300054 Expansion (Metastatic Cutaneous Melanoma)

LY3300054 given IV on day 1 and day 15 of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

LY3300054 Expansion (MSI-H Solid Tumors)

LY3300054 given IV on day 1 and day 15 of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

: LY3300054 + Abemaciclib (HR+, HER2- Breast Cancer) Expansion

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

Abemaciclib

Intervention Type: DRUG

Administered orally

LY3300054 + LY3321367 Expansion (PD-1/PD-L1 Naïve, MSI-H)

LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

LY3321367

Intervention Type: DRUG

Administered IV

LY3300054 + LY3321367 Expansion

LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

LY3321367

Intervention Type: DRUG

Administered IV

LY3300054 + Merestinib (Pancreatic Cancer) Expansion

LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.

Group Type: EXPERIMENTAL

LY3300054

Intervention Type: DRUG

Administered IV

Merestinib

Intervention Type: DRUG

Administered orally

Interventions

LY3300054

Administered IV

Intervention Type: DRUG

Ramucirumab

Administered IV

Intervention Type: DRUG

Abemaciclib

Administered orally

Intervention Type: DRUG

Merestinib

Administered orally

Intervention Type: DRUG

LY3321367

Administered IV

Intervention Type: DRUG

Other Intervention Names

LY3009806; LY2835219; LY2801653

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

Locations

Tennessee Oncology PLLC

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

The START Center for Cancer Care

San Antonio, Texas, United States

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Princess Margaret Hospital

Toronto, Ontario, Canada

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, , France

Gustave Roussy

Villejuif, , France

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Hospital Madrid Norte Sanchinarro

Madrid, , Spain

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Countries

United States; Belgium; Canada; France; South Korea; Spain; Taiwan

References

Hollebecque A, Chung HC, de Miguel MJ, Italiano A, Machiels JP, Lin CC, Dhani NC, Peeters M, Moreno V, Su WC, Chow KH, Galvao VR, Carlsen M, Yu D, Szpurka AM, Zhao Y, Schmidt SL, Gandhi L, Xu X, Bang YJ. Safety and Antitumor Activity of alpha-PD-L1 Antibody as Monotherapy or in Combination with alpha-TIM-3 Antibody in Patients with Microsatellite Instability-High/Mismatch Repair-Deficient Tumors. Clin Cancer Res. 2021 Dec 1;27(23):6393-6404. doi: 10.1158/1078-0432.CCR-21-0261. Epub 2021 Aug 31.

Reference Type: DERIVED

PMID: 34465599 (View on PubMed)

Patnaik A, Yap TA, Chung HC, de Miguel MJ, Bang YJ, Lin CC, Su WC, Italiano A, Chow KH, Szpurka AM, Yu D, Zhao Y, Carlsen M, Schmidt S, Vangerow B, Gandhi L, Xu X, Bendell J. Safety and Clinical Activity of a New Anti-PD-L1 Antibody as Monotherapy or Combined with Targeted Therapy in Advanced Solid Tumors: The PACT Phase Ia/Ib Trial. Clin Cancer Res. 2021 Mar 1;27(5):1267-1277. doi: 10.1158/1078-0432.CCR-20-2821. Epub 2020 Nov 23.

Reference Type: DERIVED

PMID: 33229456 (View on PubMed)

Related Links

https://trials.lillytrialguide.com/en-US/trial/3RHxoNIFMkcEKKcQe8uMCW

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

Other Identifiers

I8J-MC-JYCA

Identifier Type: OTHER

Identifier Source: secondary_id

2016-000440-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16088

Identifier Type: -

Identifier Source: org_study_id