A Study of LY2880070 in Participants With Advanced or Metastatic Cancer

A Phase 1b/2a Three-Part Open-Label Multicenter Study to Evaluate the Safety and Efficacy of LY2880070 as Monotherapy and in Combination With Gemcitabine in Patients With Advanced or Metastatic Cancer

The main purpose of this 3-part study is to evaluate the safety and efficacy of the study drug known as LY2880070 in participants with advanced or metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Soft Tissue Sarcoma; Breast Cancer; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer; Rectal Cancer; Triple Negative Breast Cancer; Endometrial Cancer; Colon Cancer; Solid Tumors; Pancreas Cancer
• Intervention / Treatment: Drug: LY2880070; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Estimated): 229
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network - Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Université de Montréal
• Croatia
  • Zadar, Croatia, 23000
    • General Hospital Zadar
  • Zagreb, Croatia, 10000
    • University Hospital Centre Zagreb
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii im. prof. F. Łukaszczyka
  • Gdańsk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
  • Kraków, Poland, 30-348
    • Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o. o.
  • Kraków, Poland, 31-826
    • Szpital Specjalistyczny im. L. Rydygiera w Krakowie sp. z o. o.
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Have an estimated life expectancy of greater than or equal to (≥)12 weeks
• Have adequate organ function
• Have received 1-4 prior systemic therapies for locally advanced or metastatic disease
• Agree to use medically approved contraceptives during the study and for 3 months following the last study treatment
• All females must have a negative serum pregnancy test result, and females of child-bearing potential must have a negative urine pregnancy test result, prior to the first study treatment
• Have tumor lesions considered measurable by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Must be, in the judgment of the investigator, an appropriate candidate for experimental therapy, and no standard therapy would confer clinical benefit

For Part A

• Must have evidence of cancer (solid tumors, excluding glioblastoma and primary brain tumor) that is advanced or metastatic
• For the Metabolism Phenotype Arm in Part A, participants must have a Cytochrome P450 (CYP2D6) poor metabolizer phenotype

For Part B

• Have advanced or metastatic colorectal cancer, triple negative breast cancer (per American Society of Clinical Oncology-College of American Pathology guidelines), epithelial ovarian cancer, endometrial, soft tissue sarcoma, pancreatic cancer

  • For TNBC:

    • Recurrent/refractory Triple Negative Breast Cancer (TNBC) defined as any beast cancer that expresses <1% estrogen receptor (ER) and <1% progesterone receptor (PR) and is Her2 negative

  • For Colorectal (CRC):

    • Must have histologically confirmed advanced or metastatic colorectal cancer

  • For Ovarian Cancer:

    • Must have histologically confirmed advanced or metastatic epithelial ovarian cancer
    • Must be eligible to receive Gemzar (GEM) and not refractory to GEM/carboplatin
    • Must have the ability to tolerate GEM
    • May have received GEM as previous therapy

  • For Endometrial cancer:

    • Must have histologically confirmed endometrial cancer that is metastatic or locally advanced
    • Must have failed at least 1 prior chemotherapy

  • For STS:

    • Must have histologically confirmed STS that is metastatic or locally advanced
    • Patients with gastrointestinal stromal tumors (GIST) must have failed a KIT inhibitor
    • Must have failed at least 1 prior chemotherapy

  • For Pancreatic Cancer:

    • Must have histologically confirmed pancreatic cancer that is metastatic or locally advanced
    • Must have failed at least 1 prior chemotherapy regimen
  • For Part C
  • Participants with high grade serous ovarian cancer (HGSOC) will be screened for specific genetic signatures

Exclusion Criteria:

• Have received treatment with an investigational drug which has not received regulatory approval within 21 days of first study treatment
• Have symptomatic central nervous system (CNS) metastasis
• Females who are pregnant or nursing
• Have known positive test results of human immunodeficiency virus, or have chronic active hepatitis A, B or C
• Have a corrected QT interval (QTcB) greater than (>) 470 milliseconds (msec) (female) or >450 msec (male), or a history of congenital long QT syndrome
• Have had a bone marrow transplant
• Have participated in this study, or are currently enrolled in another clinical study of an investigational medicinal product
• Have had radiation therapy to >25% of bone marrow

• For Part B

  • Have a history of another active cancer within the past year, except cervical cancer in situ, in situ carcinoma of the bladder, basal cell carcinoma of the skin, or another in situ carcinoma that is considered cured

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: LY2880070; Multiple oral doses of LY2880070 during 21-day cycles	Drug: LY2880070; Capsules
Experimental: Part A: LY2880070 with Gemcitabine; Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar
Experimental: Part A: LY2880070 (Metabolism Phenotype); Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers	Drug: LY2880070; Capsules
Experimental: Part B: LY2880070 and Gemcitabine (Breast); Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Colorectal); Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar
Experimental: Part B:LY2880070 and Gemcitabine (Ovarian); Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Endometrial); Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS)); Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Pancreatic); Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar
Experimental: Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer); Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070; Capsules; Drug: Gemcitabine; 50 to 600 milligrams per square meter of body surface area (mg/m2); Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose(s)	Baseline through Cycle 1 (Estimated up to 21 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of dose limiting toxicities (DLTs)	Baseline through Cycle 1 (Estimated up to 21 days)
Area under the plasma concentration versus time curve from time zero to 24 hours post-dose (AUC0-24)	Baseline to 24-hours post dose (up to Day 20 in Cycle 1)
Peak plasma concentration (Cmax)	Baseline to 24 hours post-dose (up to Day 20 in Cycle 1)
Time to reach maximum plasma concentration (tmax)	Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
Change from baseline in white blood cell count	Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
Change from baseline in neutrophil count	Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
Change from baseline in lymphocyte count	Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
Number of participants with tumor response (objective response rate) as measured by the Response Evaluable Criteria in Solid Tumors (RECIST v.1.1)	Baseline to study completion (estimated up to 4 years)
Duration of objective response	Baseline to study completion (estimated up to 4 years)
Best response	Baseline to study completion (estimated up to 4 years)
Progression free survival	Baseline to study completion (estimated up to 4 years)
Overall survival	Baseline up to 1 year

Collaborators and Investigators

• Sponsor: Esperas Pharma Inc.
• Investigators: Study Director: Email: Darcy.Vincett@ozmosisresearch.ca, Esperas Pharma Inc.

Publications and helpful links

General Publications

• W.H. Miller, A.F. Shields, D. Provencher, L. Gilbert, G. Shapiro, A.M. Oza, J. Spratlin, S. Lheureux, G. Bhat, S. Salvador, P. Nunes, S. Lau, I. Weiner, J. Keene, S. Zaknoen, P. Smith, J. Stille, D. Vincett, Q.S-C. Chu, 537P A phase I/II study of oral chk1 inhibitor LY2880070 in combination with low-dose gemcitabine in patients with advanced or metastatic ovarian cancer, Annals of Oncology, Volume 33, Supplement 7, 2022, Pages S793-S794, ISSN 0923-7534, https://doi.org/10.1016/j.annonc.2022.07.665. (https://www.sciencedirect.com/science/article/pii/S0923753422025169)
• DOI: 10.1200/JCO.2020.38.15_suppl.3579 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3579-3579.
• DOI: 10.1200/JCO.2020.38.15_suppl.3581 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.

Helpful Links

• A phase 1b study of oral chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer: Abstract 2020 ASCO Annual Meeting

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2016
• Primary Completion (Actual): April 14, 2025
• Study Completion (Actual): April 14, 2025

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimated): December 16, 2015

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Advanced cancer; Pancreatic Cancer; Metastatic cancer; Pancreatic Neoplasms; Colorectal neoplasms; Triple negative breast cancer; Rectal neoplasms; Gastrointestinal stromal tumor; Recurrent cancer; Ovarian neoplasms; Triple negative breast neoplasms; Colon neoplasms
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplastic Processes; Skin Diseases; Breast Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Sarcoma; Triple Negative Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: ESPS-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No