Clinical trial NCT02784795: A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors
Official title: A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Breast Cancer
Colon Cancer
Cholangiocarcinoma
Soft Tissue Sarcoma
Keywords: Notch Inhibitor
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-05-27
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with other anticancer agents in participants with advanced or metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

* For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer.

  * For dose escalation for all combinations: The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic.
  * For Part A dose confirmation: All participants must have histological evidence of advanced or metastatic soft tissue sarcoma or breast cancer. Breast cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
  * For Part B dose confirmation: All participants must have histological evidence of advanced or metastatic colon cancer or soft tissue sarcoma. Colon cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
  * For Part C dose confirmation: All participants must have histological evidence of advanced or metastatic breast cancer and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
  * For Part D dose confirmation: All participants must have histological evidence of cholangiocarcinoma and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received \>1 line of prior systemic therapy for metastatic or resectable disease (that is, participants may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease).
  * For Part E dose confirmation: All participants must have histological evidence of locally advanced or metastatic triple negative breast cancer (TNBC) and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received \>2 lines of systemic treatment for advanced or metastatic TNBC.
* Have adequate organ function.
* Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
* Have discontinued all previous therapies for cancer.

Exclusion Criteria:

* Have current acute leukemia.
* Have current or recent (within 3 months of study drug administration) gastrointestinal disease with chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of LY3039478
timeFrame: Cycle 1 (up to 28 Days)
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve (AUC) of LY3039478 in Combination with Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
measure: PK: AUC of Taladegib and its Active Metabolite LSN3185556, in Combination with LY3039478
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
measure: PK: AUC of LY3023414 in Combination with LY3039478
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
measure: PK: AUC of Abemaciclib and its Major Active Metabolites LSN2839567 and LSN3106726, in Combination with LY3039478
timeFrame: Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
measure: Duration of Response (DoR)
timeFrame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Estimated up to 12 Months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to Objective Disease Progression or Death (Estimated up to 12 Months)
Other outcomes:
Locations:
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: København Ø
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Madrid Norte Sanchinarro
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Massard C, Cassier PA, Azaro A, Anderson B, Yuen E, Yu D, Oakley G 3rd, Benhadji KA, Pant S. A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors. Cancer Chemother Pharmacol. 2022 Oct;90(4):335-344. doi: 10.1007/s00280-022-04461-z. Epub 2022 Aug 28.
citation: Azaro A, Massard C, Tap WD, Cassier PA, Merchan J, Italiano A, Anderson B, Yuen E, Yu D, Oakley G 3rd, Benhadji KA, Pant S. A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors. Invest New Drugs. 2021 Aug;39(4):1089-1098. doi: 10.1007/s10637-021-01094-6. Epub 2021 Mar 8.