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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)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02791334
Recruitment Status : Active, not recruiting
First Posted : June 6, 2016
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment 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 Drug: LY3321367 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 215 participants
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)
Actual Study Start Date : January 1, 2016
Actual Primary Completion Date : May 22, 2020
Estimated Study Completion Date : December 6, 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

Arm Intervention/treatment
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 + 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.
Drug: LY3300054
Administered IV

Drug: LY3321367
Administered IV

Experimental: LY3300054 + LY3321367 Expansion
LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
Drug: LY3300054
Administered IV

Drug: LY3321367
Administered IV

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




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

Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3300054 [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  2. PK: Cmax of Ramucirumab [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  3. PK: Cmax of Abemaciclib [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  4. PK: Cmax of Merestinib [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  5. PK: Cmax of LY3321367 [ Time Frame: Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months) ]
  6. 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 ) ]
  7. Progression Free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death (Approximately 12 Months) ]
  8. 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) ]
  9. Time to Response (TTR) [ Time Frame: Baseline to Date of CR or PR (Approximately 6 Months) ]
  10. 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) ]


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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.
  • 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.

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


Locations
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United States, Tennessee
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, United States, 37203
Tennessee Oncology PLLC
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
The START Center for Cancer Care
San Antonio, Texas, United States, 78229
Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, 2650
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5TY 2M9
France
Institut Bergonie
Bordeaux, France, 33076
Gustave Roussy
Villejuif Cedex, France, 94805
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Severance Hospital Yonsei University Health System
Seoul, Korea, Republic of, 03722
Spain
Fundacion Jimenez Diaz
Madrid, Spain, 28040
Hospital Madrid Norte Sanchinarro
Madrid, Spain, 28050
Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan, 70403
National Taiwan University Hospital
Taipei, Taiwan, 10048
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02791334    
Other Study ID Numbers: 16088
I8J-MC-JYCA ( Other Identifier: Eli Lilly and Company )
2016-000440-33 ( EudraCT Number )
First Posted: June 6, 2016    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 15, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
PDL1
PD-L1
Additional relevant MeSH terms:
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Neoplasms
Microsatellite Instability
Genomic Instability
Pathologic Processes
Ramucirumab
Antineoplastic Agents