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Solid TumorPhase 1PACTNCT02791334

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

A Phase 1 study testing LY3300054, Ramucirumab and Abemaciclib in people with Solid Tumor and Microsatellite Instability-High (MSI-H) Solid Tumors, run by Eli Lilly and Company at 14 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LY3300054, Ramucirumab and Abemaciclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
164 participants
Where
14 sitesin 7 countries
Study dates
29 Jun 2016to 27 Jun 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 30Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

14 sites in 7 countries.

14 sites in 7 countries

United States3 sites

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Tennessee Oncology PLLC

    Nashville, Tennessee, 37203

  • The START Center for Cancer Care

    San Antonio, Texas, 78229

Other trials in United States

Belgium2 sites

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

  • Universitair Ziekenhuis Antwerpen

    Edegem, 2650

Other trials in Belgium

France2 sites

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

    Bordeaux, 33076

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

South Korea2 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

Other trials in South Korea

Spain2 sites

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Madrid Norte Sanchinarro

    Madrid, 28050

Other trials in Spain

Taiwan2 sites

  • National Cheng Kung University Hospital

    Tainan, 70403

  • National Taiwan University Hospital

    Taipei, 10048

Other trials in Taiwan

Canada1 site

  • Princess Margaret Hospital

    Toronto, Ontario, M5TY 2M9

Other trials in Canada

About this study

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)

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.

Being tested
LY3300054, Ramucirumab, Abemaciclib, Merestinib, LY3321367
Keywords
PDL1, PD-L1
Medical subject headings
Melanoma, Pancreatic Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LY3300054Drug

    Administered IV

  • RamucirumabDrug

    Also called LY3009806

    Administered IV

  • AbemaciclibDrug

    Also called LY2835219

    Administered orally

  • MerestinibDrug

    Also called LY2801653

    Administered orally

  • LY3321367Drug

    Administered IV

Study groups in NCT02791334
Study groupRoleWhat they receive
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.
Receives: Drug: 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.
Receives: Drug: LY3300054; Drug: Ramucirumab
Abemaciclib + LY3300054ExperimentalLY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
Receives: Drug: LY3300054; Drug: 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.
Receives: Drug: LY3300054; Drug: 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.
Receives: Drug: LY3300054; Drug: Abemaciclib
LY3300054 + MerestinibExperimentalLY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
Receives: Drug: LY3300054; Drug: Merestinib
LY3300054 Expansion (Metastatic Cutaneous Melanoma)ExperimentalLY3300054 given IV on day 1 and day 15 of a 28 day cycle.
Receives: Drug: LY3300054
LY3300054 Expansion (MSI-H Solid Tumors)ExperimentalLY3300054 given IV on day 1 and day 15 of a 28 day cycle.
Receives: Drug: 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.
Receives: Drug: LY3300054; Drug: 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.
Receives: Drug: LY3300054; Drug: LY3321367
LY3300054 + LY3321367 ExpansionExperimentalLY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
Receives: Drug: LY3300054; Drug: 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.
Receives: Drug: LY3300054; Drug: Merestinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs)

    Measured: Baseline through Cycle 1 (Approximately 28 Days)

Secondary outcomes (10)

  1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3300054

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

  2. PK: Cmax of Ramucirumab

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

  3. PK: Cmax of Abemaciclib

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

  4. PK: Cmax of Merestinib

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

  5. PK: Cmax of LY3321367

    Measured: 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)

    Measured: Baseline to Measured Progressive Disease (Approximately 6 Months )

  7. Progression Free Survival (PFS)

    Measured: Baseline to Measured Progressive Disease or Death (Approximately 12 Months)

  8. Duration of Response (DoR)

    Measured: 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)

    Measured: 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

    Measured: Baseline to Measured Progressive Disease (Approximately 6 Months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2016 (estimated)
  2. Study start29 Jun 2016
  3. Primary completion22 May 2020
  4. Study completion27 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02791334
Sponsor's protocol ID
16088
Other IDs
I8J-MC-JYCA, 2016-000440-33, 2016
Acronym
PACT
Status last verified
Sep 2024
First submitted
1 Jun 2016
Last updated
27 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 34465599

  • 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.

    PubMed 33229456

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY3300054, Ramucirumab and Abemaciclib in people with Solid Tumor and Microsatellite Instability-High (MSI-H) Solid Tumors, run by Eli Lilly and Company at 14 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Belgium, France, South Korea, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs) (time frame: Baseline through Cycle 1 (Approximately 28 Days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02791334, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2024.

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