Clinical Trials /

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

NCT02791334

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

  • ORG STUDY ID: 16088
  • SECONDARY ID: I8J-MC-JYCA
  • SECONDARY ID: 2016-000440-33
  • NCT ID: NCT02791334

Conditions

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

Interventions

DrugSynonymsArms
LY3300054LY3300054
RamucirumabLY3009806LY3300054 + Ramucirumab
AbemaciclibLY2835219Abemaciclib + LY3300054
MerestinibLY2801653LY3300054 + Merestinib
LY3321367LY3300054 + LY3321367 Expansion (PD-1/PD-L1 Naïve, MSI-H)

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.

Trial Arms

NameTypeDescriptionInterventions
LY3300054ExperimentalLY3300054 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.
  • LY3300054
LY3300054 + RamucirumabExperimentalLY3300054 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.
  • LY3300054
  • Ramucirumab
Abemaciclib + LY3300054ExperimentalLY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
  • LY3300054
  • Abemaciclib
LY3300054 + Abemaciclib (Concurrent Dosing)ExperimentalLY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
  • LY3300054
  • Abemaciclib
LY3300054 + AbemaciclibExperimentalLY3300054 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.
  • LY3300054
  • Abemaciclib
LY3300054 + MerestinibExperimentalLY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
  • LY3300054
  • Merestinib
LY3300054 Expansion (Metastatic Cutaneous Melanoma)ExperimentalLY3300054 given IV on day 1 and day 15 of a 28 day cycle.
  • LY3300054
LY3300054 Expansion (MSI-H Solid Tumors)ExperimentalLY3300054 given IV on day 1 and day 15 of a 28 day cycle.
  • LY3300054
: LY3300054 + Abemaciclib (HR+, HER2- Breast Cancer) ExpansionExperimentalLY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
  • LY3300054
  • Abemaciclib
LY3300054 + LY3321367 Expansion (PD-1/PD-L1 Naïve, MSI-H)ExperimentalLY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
  • LY3300054
  • LY3321367
LY3300054 + LY3321367 ExpansionExperimentalLY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
  • LY3300054
  • LY3321367
LY3300054 + Merestinib (Pancreatic Cancer) ExpansionExperimentalLY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
  • LY3300054
  • Merestinib

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs)
Time Frame:Baseline through Cycle 1 (Approximately 28 Days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3300054
Time Frame:Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Safety Issue:
Description:
Measure:PK: Cmax of Ramucirumab
Time Frame:Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Safety Issue:
Description:
Measure:PK: Cmax of Abemaciclib
Time Frame:Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Safety Issue:
Description:
Measure:PK: Cmax of Merestinib
Time Frame:Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Safety Issue:
Description:
Measure:PK: Cmax of LY3321367
Time Frame:Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months)
Safety Issue:
Description:
Measure: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 )
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Baseline to Measured Progressive Disease or Death (Approximately 12 Months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Time to Response (TTR)
Time Frame:Baseline to Date of CR or PR (Approximately 6 Months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • PDL1
  • PD-L1

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