Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies

• ClinicalTrials.gov Identifier: NCT02711137
• Recruitment Status: Terminated
• First Posted: March 17, 2016
• Last Update Posted: February 17, 2020
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: March 9, 2016
• First Posted Date: March 17, 2016
• Last Update Posted Date: February 17, 2020
• Study Start Date: May 18, 2016
• Actual Primary Completion Date: February 13, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 27, 2017): Safety and tolerability of INCB057643 as monotherapy and in combination with standard of care (SOC) agents in patients with advanced malignancies; assessed by clinical laboratory assessments, physical examinations, 12 lead ECGs, and adverse events (AEs) [ Time Frame: From screening through at least 30 days after end of treatment, up to approximately 24 months ]
• Original Primary Outcome Measures (submitted: March 12, 2016): Safety and tolerability of INCB057643 as assessed by clinical laboratory assessments, physical examinations, 12 lead ECGs, and adverse events (AEs) [ Time Frame: From screening through at least 30 days after end of treatment, up to approximately 24 months ]

Current Secondary Outcome Measures (submitted: November 12, 2019)

• Pharmacokinetics of INCB057643 as monotherapy in the fasted state and in the fed state (food effect; Part 2 only) and when administered in combination with Standard of Care (SOC) agents in the fasted state assessed by plasma and urine concentrations [ Time Frame: Protocol-defined timepoints in treatment Cycle 1 and 2, up to approximately 1 month. ]
• Measurement of cellular myc protein concentrations before and after administration of INCB057643 when administered as monotherapy [ Time Frame: PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, up to approximately 1 month. ]
• Efficacy of INCB057643 when administered as monotherapy and in combination with SOC agents based on the investigator assessment of response using criteria appropriate for each disease in subjects with advanced malignancies criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]

Original Secondary Outcome Measures (submitted: March 12, 2016)

• Plasma and urine concentrations of INCB057643 when administered in the fasted state [ Time Frame: Protocol-defined timepoints in treatment Cycle 1, up to approximately 1 month. PK in urine over 8-hour interval postdose ]
• Plasma concentrations of INCB057643 plasma when administered in the fed state [ Time Frame: Protocol-defined timepoints in treatment Cycles 1 and 2, up to approximately 1 month ]
• Measurement of cellular myc protein concentrations before and after administration of INCB057643 [ Time Frame: PD in plasma at 0.5, 1, 2, 4, 6, 8, and 24 hours postdose, up to approximately 1 month. Sparse correlative whole blood and plasma up to approximately 6 months ]
• Efficacy assessed by objective response rate (ORR) per disease-specific response criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
• Efficacy assessed by progression-free survival (PFS) per disease-specific response criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
• Efficacy assessed by duration of response per disease-specific response criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
• Efficacy assessed by overall survival per disease-specific response criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]

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

Descriptive Information

• Brief Title: Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
• Official Title: A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies

Brief Summary

The purpose of the Study is to select a dose and assess the safety and tolerability of INCB057643 as a monotherapy (Part 1 and Part 2) and in combination with standard-of-care (SOC) agents (Part 3 and Part 4) for subjects with advanced malignancies.

Part 1 will determine the maximum tolerated dose of INCB057643 and/or a tolerated dose that demonstrates sufficient pharmacologic activity. Part 2 will further evaluate the safety, preliminary efficacy, PK, and PD of the dose(s) selected in Part 1 in select tumor types including solid tumors, lymphomas and other hematologic malignancies. Part 3 will determine the tolerated dose of INCB057643 in combination with select SOC agents; and assess the safety and tolerability of the combination therapy in select advanced solid tumors and hematologic malignancies. Part 4 will further evaluate the safety, preliminary efficacy, PK, and PD of the selected dose combination from Part 3 in 4 specific advanced solid tumor and hematologic malignancies.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

• Drug: INCB057643
  Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
• Drug: INCB057643
  Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 3), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 4).
• Drug: Gemcitabine
  Standard of Care (SOC) agents
• Drug: Paclitaxel
  Standard of Care (SOC) agents
• Drug: Rucaparib
  Standard of Care (SOC) agents
• Drug: Abiraterone
  Standard of Care (SOC) agents
• Drug: Ruxolitinib
  Standard of Care (SOC) agents
• Drug: Azacitidine
  Standard of Care (SOC) agents

Study Arms

• Experimental: INCB057643
  Intervention: Drug: INCB057643
• Experimental: INCB057643 + Standard of Care (SOC) agents
  Interventions:

  • Drug: INCB057643
  • Drug: Gemcitabine
  • Drug: Paclitaxel
  • Drug: Rucaparib
  • Drug: Abiraterone
  • Drug: Ruxolitinib
  • Drug: Azacitidine

• Publications *: Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257. doi: 10.1158/1078-0432.CCR-18-4071. Epub 2019 Sep 16.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 16, 2018): 136
• Original Estimated Enrollment (submitted: March 12, 2016): 155
• Actual Study Completion Date: February 13, 2019
• Actual Primary Completion Date: February 13, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of relapsed or refractory advanced or metastatic malignancies:

  • Part 1: solid tumors or lymphomas, or hematologic malignancies
  • Part 2: histologically confirmed disease in specific tumor types
  • Part 3: advanced solid tumor or hematologic malignancy
  • Part 4: select advanced solid tumor or hematologic malignancy
• For Part 1 and 2, subjects must have progressed following at least 1 line of prior therapy and there is no further established therapy that is known to provide clinical benefit (including subjects who are intolerant to the established therapy)
• For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.
• Life expectancy > 12 weeks, for MF subjects in Parts 3 and 4, life expectancy > 24 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status

  • Parts 1 and 3: 0 or 1
  • Parts 2 and 4: 0, 1, or 2
• Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

• Inadequate bone marrow function per protocol-specified hemoglobin, platelet count, and absolute neutrophil count
• Inadequate organ function per protocol-specified total bilirubin, AST and ALT, creatinine clearance and alkaline phosphatase.
• Receipt of anticancer medications or investigational drugs within protocol-specified intervals
• Unless approved by the medical monitor, may not have received an allogeneic hematopoietic stem cell transplant within 6 months before treatment, or have active graft-versus-host-disease following allogeneic transplant
• Unless approved by the medical monitor, may not have received autologous hematopoietic stem cell transplant within 3 months before treatment
• Any unresolved toxicity ≥ Grade 2 (except stable Grade 2 peripheral neuropathy or alopecia) from previous anticancer therapy
• Radiotherapy within the 2 weeks before initiation of treatment. Palliative radiation treatment to nonindex or bone lesions performed less than 2 weeks before treatment initiation may be considered with medical monitor approval
• Currently active and uncontrolled infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment
• Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
• History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
• Type 1 diabetes or uncontrolled Type 2 diabetes
• HbA1c of ≥ 8% (all subjects will have HbA1c test at screening)
• Any sign of clinically significant bleeding
• Coagulation panel within protocol-specified parameters

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, United States

Administrative Information

• NCT Number: NCT02711137
• Other Study ID Numbers: INCB 57643-101
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Incyte Corporation
• Study Sponsor: Incyte Corporation
• Collaborators: Not Provided

Investigators

• Study Director: Fred Zheng, MD, PhD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: February 2020