A Study of LY2880070 in Participants With Advanced or Metastatic Cancer

• ClinicalTrials.gov Identifier: NCT02632448
• Recruitment Status: Recruiting
• First Posted: December 16, 2015
• Last Update Posted: March 29, 2024
• Sponsor: Esperas Pharma Inc.
• Information provided by (Responsible Party): Esperas Pharma Inc.

Tracking Information

• First Submitted Date: December 14, 2015
• First Posted Date: December 16, 2015
• Last Update Posted Date: March 29, 2024
• Actual Study Start Date: May 16, 2016
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 7, 2019): Maximum Tolerated Dose(s) [ Time Frame: Baseline through Cycle 1 (Estimated up to 21 days) ]
• Original Primary Outcome Measures (submitted: December 15, 2015): Maximum Tolerated Dose [ Time Frame: Baseline through Cycle 1 (Estimated up to 21 days) ]

Current Secondary Outcome Measures (submitted: June 13, 2017)

• Number of dose limiting toxicities (DLTs) [ Time Frame: 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) [ Time Frame: Baseline to 24-hours post dose (up to Day 20 in Cycle 1) ]
• Peak plasma concentration (Cmax) [ Time Frame: Baseline to 24 hours post-dose (up to Day 20 in Cycle 1) ]
• Time to reach maximum plasma concentration (tmax) [ Time Frame: Baseline to 24 hours post dose (up to Day 20 in Cycle 1) ]
• Change from baseline in white blood cell count [ Time Frame: Baseline to 24 hours post dose (up to Day 20 in Cycle 1) ]
• Change from baseline in neutrophil count [ Time Frame: Baseline to 24 hours post dose (up to Day 20 in Cycle 1) ]
• Change from baseline in lymphocyte count [ Time Frame: 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) [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Duration of objective response [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Best response [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Progression free survival [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Overall survival [ Time Frame: Baseline up to 1 year ]

Original Secondary Outcome Measures (submitted: December 15, 2015)

• Number of dose limiting toxicities (DLTs) [ Time Frame: 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) [ Time Frame: Baseline to 24-hours post dose (up to Day 19) ]
• Peak plasma concentration (Cmax) [ Time Frame: Baseline to 24 hours post-dose (up to Day 19) ]
• Time to reach maximum plasma concentration (tmax) [ Time Frame: Baseline to 24 hours post dose (up to Day 19) ]
• Change from baseline in white blood cell count [ Time Frame: Baseline to 24 hours post dose (up to Day 19) ]
• Change from baseline in neutrophil count [ Time Frame: Baseline to 24 hours post dose (up to Day 19) ]
• Change from baseline in lymphocyte count [ Time Frame: Baseline to 24 hours post dose (up to Day 19) ]
• Number of participants with tumor response, as measured by the Response Evaluable Criteria in Solid Tumors (RECIST v.1.1) [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Duration of response [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Best response [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Progression free survival [ Time Frame: Baseline to study completion (estimated up to 4 years) ]
• Overall survival [ Time Frame: Baseline to study completion (estimated up to 4 years) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LY2880070 in Participants With Advanced or Metastatic Cancer
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science

Condition

• Solid Tumors
• Colorectal Cancer
• Breast Cancer
• Ovarian Cancer
• Colon Cancer
• Rectal Cancer
• Neoplasms
• Endometrial Cancer
• Soft Tissue Sarcoma
• Triple Negative Breast Cancer
• Pancreas Cancer
• Pancreatic Cancer

Intervention

• Drug: LY2880070
  Capsules
• Drug: Gemcitabine
  50 to 600 milligrams per square meter of body surface area (mg/m2)
  Other Name: Gemzar

Study Arms

• Experimental: Part A: LY2880070
  Multiple oral doses of LY2880070 during 21-day cycles
  Intervention: Drug: LY2880070
• Experimental: Part A: LY2880070 with Gemcitabine
  Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine
• Experimental: Part A: LY2880070 (Metabolism Phenotype)
  Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers
  Intervention: Drug: LY2880070
• Experimental: Part B: LY2880070 and Gemcitabine (Breast)
  Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine
• Experimental: Part B: LY2880070 and Gemcitabine (Colorectal)
  Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine
• Experimental: Part B:LY2880070 and Gemcitabine (Ovarian)
  Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine
• Experimental: Part B: LY2880070 and Gemcitabine (Endometrial)
  Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine
• Experimental: Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS))
  Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine
• Experimental: Part B: LY2880070 and Gemcitabine (Pancreatic)
  Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine
• Experimental: Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)
  Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
  Interventions:

  • Drug: LY2880070
  • Drug: Gemcitabine

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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 11, 2023): 229
• Original Estimated Enrollment (submitted: December 15, 2015): 84
• Estimated Study Completion Date: September 30, 2025
• Estimated Primary Completion Date: September 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Esperas Pharma Inc.

• Listed Location Countries: Canada, Croatia, Poland, United States

Administrative Information

• NCT Number: NCT02632448
• Other Study ID Numbers: ESPS-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Esperas Pharma Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Esperas Pharma Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Email: Darcy.Vincett@ozmosisresearch.ca; Esperas Pharma Inc.

• PRS Account: Esperas Pharma Inc.
• Verification Date: March 2024