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

This study is currently recruiting participants.
Verified November 2017 by Eli Lilly and Company
Sponsor:
ClinicalTrials.gov Identifier:
NCT02791334
First Posted: June 6, 2016
Last Update Posted: November 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Eli Lilly and Company
  Purpose
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.

Condition Intervention Phase
Solid Tumor Microsatellite Instability-High (MSI-H) Solid Tumors Cutaneous Melanoma Pancreatic Cancer Breast Cancer (HR+HER2-) Drug: LY3300054 Drug: Ramucirumab Drug: Abemaciclib Drug: Merestinib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline through Cycle 1 (Approximately 28 Days) ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3300054 [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  • PK: Cmax of Ramucirumab [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  • PK: Cmax of Abemaciclib [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  • PK: Cmax of Merestinib [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  • Objective Response Rate (ORR): Proportion of Participants With a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Measured Progressive Disease (Approximately 6 Months ) ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death (Approximately 12 Months) ]
  • Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Measured Progressive Disease or Death Due to Any Cause (Approximately 12 Months) ]
  • Time to Response (TTR) [ Time Frame: Baseline to Date of CR or PR (Approximately 6 Months) ]
  • Disease Control Rate (DCR): Proportion of Participants who Exhibit Stable Disease (SD), CR or PR [ Time Frame: Baseline to Measured Progressive Disease (Approximately 6 Months) ]

Estimated Enrollment: 115
Actual Study Start Date: June 29, 2016
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: LY3300054
Administered IV
Experimental: 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.
Drug: LY3300054
Administered IV
Drug: Ramucirumab
Administered IV
Other Name: LY3009806
Experimental: Abemaciclib + LY3300054
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
Drug: LY3300054
Administered IV
Drug: Abemaciclib
Administered orally
Other Name: LY2835219
Experimental: 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.
Drug: LY3300054
Administered IV
Drug: Abemaciclib
Administered orally
Other Name: LY2835219
Experimental: 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.
Drug: LY3300054
Administered IV
Drug: Abemaciclib
Administered orally
Other Name: LY2835219
Experimental: LY3300054 + Merestinib
LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
Drug: LY3300054
Administered IV
Drug: Merestinib
Administered orally
Other Name: LY2801653
Experimental: LY3300054 Expansion (Metastatic Cutaneous Melanoma)
LY3300054 given IV on day 1 and day 15 of a 28 day cycle.
Drug: LY3300054
Administered IV
Experimental: LY3300054 Expansion (MSI-H Solid Tumors)
LY3300054 given IV on day 1 and day 15 of a 28 day cycle.
Drug: LY3300054
Administered IV
Experimental: : 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.
Drug: LY3300054
Administered IV
Drug: Abemaciclib
Administered orally
Other Name: LY2835219
Experimental: 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.
Drug: LY3300054
Administered IV
Drug: Merestinib
Administered orally
Other Name: LY2801653

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP).
  • 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 ≤2.5*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 Phase 1b LY3300054 monotherapy or combination therapy, no prior treatment with a PD-1 or PD-L1 agent is allowed.
  • 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 participants participating ONLY in the Phase 1b expansion: have submitted tissue sample from either a newly obtained core or excisional biopsy of a tumor lesion (preferred) or a recent biopsy since last documented progression of disease.
    • For those participating ONLY in Phase 1b abemaciclib or merestinib 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02791334


Contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
United States, Tennessee
Tennessee Oncology PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-329-7274      
Principal Investigator: J C Bendell         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact    713-745-6754      
Principal Investigator: Timothy Yap         
The START Center for Cancer Care Recruiting
San Antonio, Texas, United States, 78229
Contact    210-593-5270      
Principal Investigator: Amita Patnaik         
Belgium
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Brussels, Belgium, 1200
Contact: Eli Lilly and Company         
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Edegem, Belgium, 2650
Contact: Eli Lilly and Company         
Canada
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Recruiting
Calgary, Canada, T2N 4N2
Contact: Eli Lilly and Company         
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Recruiting
Toronto, Canada, M5G 2M9
Contact: Eli Lilly and Company         
France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Bordeaux, France, 33076
Contact: Eli Lilly and Company         
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Villejuif, France, 94805
Contact: Eli Lilly and Company         
Korea, Republic of
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Recruiting
Seoul, Korea, Republic of, 03080
Contact: Eli Lilly and Company         
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Recruiting
Seoul, Korea, Republic of, 03722
Contact: Eli Lilly and Company         
Spain
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Madrid, Spain, 28050
Contact: Eli Lilly and Company         
Taiwan
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Recruiting
Tainan, Taiwan, 70403
Contact: Eli Lilly and Company         
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Recruiting
Taipei, Taiwan, 10048
Contact: Eli Lilly and Company         
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

Additional Information:
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02791334     History of Changes
Other Study ID Numbers: 16088
I8J-MC-JYCA ( Other Identifier: Eli Lilly and Company )
2016-000440-33 ( EudraCT Number )
First Submitted: June 1, 2016
First Posted: June 6, 2016
Last Update Posted: November 8, 2017
Last Verified: November 2017

Keywords provided by Eli Lilly and Company:
PDL1
PD-L1

Additional relevant MeSH terms:
Neoplasms
Pancreatic Neoplasms
Melanoma
Microsatellite Instability
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Genomic Instability
Pathologic Processes
Antibodies
Ramucirumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents