An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies

NCT02265510 | Terminated Phase 1 Results

• 1 other identifier: INCB 52793-101
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 14

Brief Summary

This was a study of INCB052793 given to patients with advanced malignancies that was to be conducted in three phases; Phase 1a (Monotherapy) and Phase 1b (Combination Therapy) and Phase 2 (Combination therapy of INCB052793 with azacitidine and itacitinib with azacitidine). Phase 1 had two parts; a dose escalation (Part 1) and an expansion (Part 2).

Conditions

Solid Tumors; Advanced Malignancies; Metastatic Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

  An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug.

  From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 3.4 years)

• Phase 2: Objective Response Rate (ORR) in Hematological Malignancies

  ORR is defined as the proportion of participants who achieved complete response (CR), CR with incomplete hematologic recovery (CRi), partial response (PR), or hematologic improvement (HI), using the IWG response criteria.

  Baseline through end of study (Up to approximately 4.5 years)

Secondary Outcomes (21)

• Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment

  Baseline through end of study (Up to approximately 4.5 years)

• Phase 2: Number of Participants With at Least One TEAE and SAE

  From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 1.3 years)

• Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793

  Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2

• Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793

  Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2

• Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793

  Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2

Study Arms (3)

Phase 1a: INCB052793 Monotherapy

EXPERIMENTAL

Drug: INCB052793

Phase 1b: INCB052793 Combination Therapy

EXPERIMENTAL

Drug: gemcitabine; Drug: nab-paclitaxel; Drug: dexamethasone; Drug: Carfilzomib; Drug: bortezomib; Drug: lenalidomide; Drug: azacitidine; Drug: INCB052793; Drug: pomalidomide; Drug: INCB050465

Phase 2: INCB052793 and itacitinib Combination Therapy

EXPERIMENTAL

Drug: azacitidine; Drug: INCB052793; Drug: INCB039110

Interventions

INCB052793 DRUG

Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.

Phase 1a: INCB052793 Monotherapy

gemcitabine DRUG

Gemcitabine administered intravenously over 30 minutes at the protocol-specified dose and frequency.

Also known as: Gemzar®

Phase 1b: INCB052793 Combination Therapy

nab-paclitaxel DRUG

nab-paclitaxel administered intravenously over 30 minutes at the protocol-specified dose and frequency.

Also known as: Abraxane®

Phase 1b: INCB052793 Combination Therapy

dexamethasone DRUG

Dexamethasone administered orally at the protocol-specified dose and frequency.

Phase 1b: INCB052793 Combination Therapy

Carfilzomib DRUG

Carfilzomib administered intravenously at the protocol-specified dose and frequency.

Also known as: Kyprolis®

Phase 1b: INCB052793 Combination Therapy

bortezomib DRUG

Bortezomib administered intravenously or subcutaneously at the protocol-specified dose and frequency.

Also known as: Velcade®

Phase 1b: INCB052793 Combination Therapy

lenalidomide DRUG

Lenalidomide administered orally at the protocol-specified dose and frequency.

Also known as: Revlimid®

Phase 1b: INCB052793 Combination Therapy

azacitidine DRUG

Azacitidine administered subcutaneously at the protocol-specified dose and frequency.

Also known as: Vidaza®

Phase 1b: INCB052793 Combination Therapy; Phase 2: INCB052793 and itacitinib Combination Therapy

pomalidomide DRUG

Pomalidomide administered orally at the protocol-specified dose and frequency.

Also known as: Pomalyst®

Phase 1b: INCB052793 Combination Therapy

INCB050465 DRUG

INCB050465 tablets administered orally at the protocol specified dose strength and frequency.

Phase 1b: INCB052793 Combination Therapy

INCB039110 DRUG

INCB039110 tablets administered orally at the protocol specified dose strength and frequency.

Also known as: itacitinib

Phase 2: INCB052793 and itacitinib Combination Therapy

Eligibility Criteria

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

You may qualify if:

• Phase 1a
• Aged 18 years or older
• Histologically or cytologically confirmed solid tumor or hematologic malignancy
• Life expectancy of 12 weeks or longer
• Must have received ≥ 1 prior treatment regimen
• Must not be a candidate for potentially curative or standard of care approved therapy
• Phase 1b
• Aged 18 years or older
• Cohort A: Histologically or cytologically confirmed pancreatic adenocarcinoma, triple-negative breast cancer, urothelial cancer with at least 1 measurable or evaluable target lesion
• Cohorts B, C, D, E and G: Histologically confirmed multiple myeloma and measureable/evaluable disease
• Cohort F: Confirmed acute myeloid leukemia or myelodysplastic syndrome
• Cohort H: Individuals diagnosed with lymphoma
• Prior therapy:
• Cohort A: No more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy)
• Cohorts B, C, D, E and G: Must have relapsed from or have been refractory to ≥ 2 prior treatment regimens

You may not qualify if:

• Prior receipt of a JAK1 inhibitor (Phase 1a only)
• Known active central nervous system metastases and/or carcinomatous meningitis
• Eastern Cooperative Oncology Group (ECOG) performance status \> 2
• Any known contraindications to the use of gemcitabine, nab-paclitaxel, dexamethasone, carfilzomib, bortezomib, lenalidomide, azacitidine, pomalidomide or PI3Kδ inhibitor (Phase 1b and Phase 2 only, as appropriate to treatment cohort)
• Known human immunodeficiency virus infection, or evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (14)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

West Hollywood, California, United States

Location

Unknown Facility

New Haven, Connecticut, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Hackensack, New Jersey, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

Greenville, South Carolina, United States

Location

Site 2

Nashville, Tennessee, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Dexamethasone; carfilzomib; Bortezomib; Lenalidomide; Azacitidine; pomalidomide; parsaclisib; INCB039110; itacitinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aza Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Ekaterine Asatiani, M.D.

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 29, 2014
• First Posted: October 16, 2014
• Study Start: September 10, 2014
• Primary Completion: February 27, 2019
• Study Completion: February 27, 2019
• Last Updated: April 17, 2020
• Results First Posted: April 17, 2020

Record last verified: 2020-04

Locations

US (14)