A Study of LY2880070 in Participants With Advanced or Metastatic Cancer

NCT02632448 | Completed Phase 1 FDA Drug

• 1 other identifier: ESPS-001
• Study Type: interventional
• Target: 229
• Locations: 4 countries
• Sites: 16

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.

Conditions

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

Keywords

Metastatic cancer; Advanced cancer; Recurrent cancer; Colorectal neoplasms; Triple negative breast cancer; Ovarian neoplasms; Colon neoplasms; Rectal neoplasms; Triple negative breast neoplasms; Gastrointestinal stromal tumor; Pancreatic Neoplasms; Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose(s)

  Baseline through Cycle 1 (Estimated up to 21 days)

Secondary Outcomes (12)

• 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)

Study Arms (10)

Part A: LY2880070

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles

Drug: LY2880070

Part A: LY2880070 with Gemcitabine

EXPERIMENTAL

Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles

Drug: LY2880070; Drug: Gemcitabine

Part A: LY2880070 (Metabolism Phenotype)

EXPERIMENTAL

Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers

Drug: LY2880070

Part B: LY2880070 and Gemcitabine (Breast)

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Drug: LY2880070; Drug: Gemcitabine

Part B: LY2880070 and Gemcitabine (Colorectal)

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Drug: LY2880070; Drug: Gemcitabine

Part B:LY2880070 and Gemcitabine (Ovarian)

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Drug: LY2880070; Drug: Gemcitabine

Part B: LY2880070 and Gemcitabine (Endometrial)

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Drug: LY2880070; Drug: Gemcitabine

Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS))

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Drug: LY2880070; Drug: Gemcitabine

Part B: LY2880070 and Gemcitabine (Pancreatic)

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Drug: LY2880070; Drug: Gemcitabine

Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)

EXPERIMENTAL

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Drug: LY2880070; Drug: Gemcitabine

Interventions

LY2880070 DRUG

Capsules

Part A: LY2880070; Part A: LY2880070 (Metabolism Phenotype); Part A: LY2880070 with Gemcitabine; Part B: LY2880070 and Gemcitabine (Breast); Part B: LY2880070 and Gemcitabine (Colorectal); Part B: LY2880070 and Gemcitabine (Endometrial); Part B: LY2880070 and Gemcitabine (Pancreatic); Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS)); Part B:LY2880070 and Gemcitabine (Ovarian); Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)

Gemcitabine DRUG

50 to 600 milligrams per square meter of body surface area (mg/m2)

Also known as: Gemzar

Part A: LY2880070 with Gemcitabine; Part B: LY2880070 and Gemcitabine (Breast); Part B: LY2880070 and Gemcitabine (Colorectal); Part B: LY2880070 and Gemcitabine (Endometrial); Part B: LY2880070 and Gemcitabine (Pancreatic); Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS)); Part B:LY2880070 and Gemcitabine (Ovarian); Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Esperas Pharma Inc.: lead

Study Sites (16)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network - Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 0A9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

General Hospital Zadar

Zadar, 23000, Croatia

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Centrum Onkologii im. prof. F. Łukaszczyka

Bydgoszcz, 85-796, Poland

Location

Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz

Gdansk, 80-214, Poland

Location

Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o. o.

Krakow, 30-348, Poland

Location

Szpital Specjalistyczny im. L. Rydygiera w Krakowie sp. z o. o.

Krakow, 31-826, Poland

Location

Related Publications (4)

• 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)

  RESULT

• DOI: 10.1200/JCO.2020.38.15_suppl.3579 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3579-3579.

  RESULT

• DOI: 10.1200/JCO.2020.38.15_suppl.3581 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.

  RESULT

• Huffman BM, Feng H, Parmar K, Wang J, Kapner KS, Kochupurakkal B, Martignetti DB, Sadatrezaei G, Abrams TA, Biller LH, Giannakis M, Ng K, Patel AK, Perez KJ, Singh H, Rubinson DA, Schlechter BL, Andrews E, Hannigan AM, Dunwell S, Getchell Z, Raghavan S, Wolpin BM, Fortier C, D'Andrea AD, Aguirre AJ, Shapiro GI, Cleary JM. A Phase I Expansion Cohort Study Evaluating the Safety and Efficacy of the CHK1 Inhibitor LY2880070 with Low-dose Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma. Clin Cancer Res. 2023 Dec 15;29(24):5047-5056. doi: 10.1158/1078-0432.CCR-23-2005.

  PMID: 37819936 DERIVED

Related 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

MeSH Terms

Conditions

Colorectal Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Neoplasms; Endometrial Neoplasms; Sarcoma; Triple Negative Breast Neoplasms; Pancreatic Neoplasms; Neoplasm Metastasis; Recurrence; Gastrointestinal Stromal Tumors

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Pancreatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Email: Darcy.Vincett@ozmosisresearch.ca

  Esperas Pharma Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2015
• First Posted: December 16, 2015
• Study Start: May 16, 2016
• Primary Completion: April 14, 2025
• Study Completion: April 14, 2025
• Last Updated: May 2, 2025

Record last verified: 2025-04

Locations

US (2); CR (2); CA (8); PL (4)