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Completed

NCT Number: NCT04148937

A Study of the CD73 Inhibitor LY3475070 Alone or in Combination With Pembrolizumab in Participants With Advanced Cancer

The reason for this study is to see if the CD73 inhibitor LY3475070 alone or in combination with pembrolizumab is safe and effective in participants with advanced cancer.

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Key information

Conditions

Advanced Cancer Adenocarcinoma Adnexal Diseases Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Ovarian Epithelial Carcinoma, Renal Cell Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Kidney Diseases Kidney Neoplasms Lung Diseases Lung Neoplasms Male Urogenital Diseases Melanoma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplastic Processes Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Ovarian Diseases Ovarian Neoplasms Pancreatic Diseases Pancreatic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Thoracic Neoplasms Triple Negative Breast Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants must have certain types of cancer such as breast cancer, pancreatic cancer, lung cancer, kidney cancer, skin cancer (melanoma), prostate cancer, and ovarian cancer
  • Participants must have stopped other forms of treatment for the cancer
  • In the expansion cohorts participants must be able and willing to provide a sample of the tumor before beginning treatment and a sample during the treatment. For certain tumor types, the result of a test on the tumor sample may exclude the participant from the study
  • Participants must not be pregnant, and must agree to use birth control
  • Participants must have progressed through or be intolerant to therapies with known clinical benefit

Exclusion criteria

  • Participants must not have a current untreated tuberculosis, lung disease, heart disease, uncontrolled HIV, autoimmune disease, active hepatitis B or C virus infection or using corticosteroids
  • Participant must not have cancer that has spread to the brain
  • Participant must not have received a vaccine within the last 30 days
  • Participant must not have had bowel obstruction within the last 6 months, or intestinal surgery
  • Participant must not have an infection that is currently being treated

Treatment and study plan

LY3475070

Drug

Administered orally

Pembrolizumab

Drug

Administered IV

Primary outcomes

  1. Number of Participants With Dose Limiting Toxicities (DLTs)

    Time frame: Up to 28 days from the first dose

    A DLT is defined as an adverse event that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events) version 5.0:

    • Grade 3 thrombocytopenia associated with clinically significant bleeding and requiring platelet transfusion or Grade 4 thrombocytopenia of any duration.
    • Grade ≥3 febrile neutropenia
    • Grade ≥3 anemia requiring a blood transfusion
    • Other Grade ≥4 toxicities, excluding few nonhematologic Toxicities
    • Any other significant toxicity deemed by the investigatory to be dose-limiting, such as: any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during 28-day DLT observation period), persistent Grade >2 toxicities causing a delay of LY3475070 study treatment >14 days during the 28-day DLT observation period.

Secondary outcomes

  1. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Eight Hours (AUC[0-8]) of LY3475070

    Time frame: Cycle 1 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose)

    PK: AUC[0-8] of LY3475070.

  2. PK: Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCtau) of LY3475070

    Time frame: Cycle 2 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose for the QD arms, Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose for the BID arms)

    PK: AUCtau of LY3475070

  3. PK: Maximum Concentration (Cmax) of LY3475070

    Time frame: Day 1 of Cycles 1 and 2 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose for the QD arms; Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose for the BID arms)

    PK: Cmax of LY3475070

  4. Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)

    Time frame: Baseline through Disease Progression or Death (Estimated at up to 10.4 Months)

    ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

  5. Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)

    Time frame: Baseline through Measured Progressive Disease (Estimated at up to 10.4 Months)

    DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

  6. Progression-Free Survival (PFS)

    Time frame: Baseline to Objective Progression or Death Due to Any Cause (Estimated at up to 10.4 Months)

    PFS is defined as the time from the date of start of treatment to the first date of the observed clinical or radiologically documented progressive disease or death due to any cause, whichever occurs first, was estimated and reported for all evaluable participants. For participants who were not known to have died or progressed as of the data-inclusion cut-off date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

A Phase 1 Multicenter Global First in Human Study of the CD73 Inhibitor LY3475070 as Monotherapy or in Combination With Pembrolizumab in Patients With Advanced Solid Malignancies

Important dates

Study start
2020
Primary completion
2021
Study completion
2022
First posted
Nov 4, 2019
Registry last updated
Apr 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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