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

NCT02791334 | Completed Phase 1 FDA Drug

• 3 other identifiers: 16088I8J-MC-JYCA2016-000440-33
• Study Type: interventional
• Target: 164
• Locations: 7 countries
• Sites: 14

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-)

Keywords

PDL1; PD-L1

Outcome Measures

Primary Outcomes (1)

• Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs)

  Baseline through Cycle 1 (Approximately 28 Days)

Secondary Outcomes (10)

• Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3300054

  Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)

• PK: Cmax of Ramucirumab

  Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)

• PK: Cmax of Abemaciclib

  Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)

• PK: Cmax of Merestinib

  Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)

• PK: Cmax of LY3321367

  Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)

Study Arms (12)

LY3300054

EXPERIMENTAL

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.

Drug: LY3300054

LY3300054 + Ramucirumab

EXPERIMENTAL

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.

Drug: LY3300054; Drug: Ramucirumab

Abemaciclib + LY3300054

EXPERIMENTAL

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

Drug: LY3300054; Drug: Abemaciclib

LY3300054 + Abemaciclib (Concurrent Dosing)

EXPERIMENTAL

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

Drug: LY3300054; Drug: Abemaciclib

LY3300054 + Abemaciclib

EXPERIMENTAL

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.

Drug: LY3300054; Drug: Abemaciclib

LY3300054 + Merestinib

EXPERIMENTAL

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

Drug: LY3300054; Drug: Merestinib

LY3300054 Expansion (Metastatic Cutaneous Melanoma)

EXPERIMENTAL

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

Drug: LY3300054

LY3300054 Expansion (MSI-H Solid Tumors)

EXPERIMENTAL

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

Drug: LY3300054

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

EXPERIMENTAL

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

Drug: LY3300054; Drug: Abemaciclib

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

EXPERIMENTAL

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

Drug: LY3300054; Drug: LY3321367

LY3300054 + LY3321367 Expansion

EXPERIMENTAL

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

Drug: LY3300054; Drug: LY3321367

LY3300054 + Merestinib (Pancreatic Cancer) Expansion

EXPERIMENTAL

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

Drug: LY3300054; Drug: Merestinib

Interventions

LY3300054 DRUG

Administered IV

: LY3300054 + Abemaciclib (HR+, HER2- Breast Cancer) Expansion; Abemaciclib + LY3300054; LY3300054; LY3300054 + Abemaciclib; LY3300054 + Abemaciclib (Concurrent Dosing); LY3300054 + LY3321367 Expansion; LY3300054 + LY3321367 Expansion (PD-1/PD-L1 Naïve, MSI-H); LY3300054 + Merestinib; LY3300054 + Merestinib (Pancreatic Cancer) Expansion; LY3300054 + Ramucirumab; LY3300054 Expansion (MSI-H Solid Tumors); LY3300054 Expansion (Metastatic Cutaneous Melanoma)

Ramucirumab DRUG

Administered IV

Also known as: LY3009806

LY3300054 + Ramucirumab

Abemaciclib DRUG

Administered orally

Also known as: LY2835219

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

Merestinib DRUG

Administered orally

Also known as: LY2801653

LY3300054 + Merestinib; LY3300054 + Merestinib (Pancreatic Cancer) Expansion

LY3321367 DRUG

Administered IV

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (14)

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Princess Margaret Hospital

Toronto, Ontario, M5TY 2M9, Canada

Location

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

Bordeaux, 33076, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 34465599 DERIVED

• 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.

  PMID: 33229456 DERIVED

Related Links

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

MeSH Terms

Conditions

Melanoma; Pancreatic Neoplasms; Breast Neoplasms

Interventions

LY3300054; Ramucirumab; abemaciclib; merestinib; LY3321367

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Breast Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 6, 2016
• Study Start: June 29, 2016
• Primary Completion: May 22, 2020
• Study Completion: June 27, 2024
• Last Updated: September 27, 2024

Record last verified: 2024-09

Locations

TW (2); FR (2); BE (2); ES (2); US (3); CA (1); KR (2)