A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB059872 in Subjects With Advanced Malignancies

Phase 1

• Conditions: Potential subjects include those with advanced or metastatic malignancies who are ineligible for all therapeutic options that are standard of care or known to confer clinical benefit, or who refuse these treatments.; MedDRA version: 20.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001710-28-NL
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-09
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 215

Inclusion Criteria

1. Male or female subjects, age 18 years or older.
2. Presence of measurable disease that has been confirmed by histology or cytology. Myelofibrosis subjects must have palpable spleen of = 5 cm below the left subcostal margin on physical examination at the screening visit.
3. The following malignancy types will be included in each of the treatment groups:
Part 1 (Dose Escalation)
Treatment Group A: AML or myelodysplastic syndrome (MDS)
Treatment Group B: SCLC (other solid tumors, eg, endocrine tumors, are allowed with medical monitor approval)
Part 2 (Dose Expansion)
Treatment Group A1: Relapsed/refractory AML or MDS
Treatment Group A2: MF (PMF, PPV-MF, and PET-MF)
Treatment Group B1: SCLC
Treatment Group B2: Ewing's sarcoma and poorly differentiated neuroendocrine tumors
Parts 3 and 4 (Combination Dose Escalation/Expansion)
Treatment Group C/C1: Relapsed/refractory AML
Treatment Group D/D1: Subjects with newly diagnosed, treatment-naive AML who are unfit to tolerate standard intensive chemotherapy at study entry
Treatment Group E/E1: SCLC previously progressed on platinum-based treatment
4. Subjects must meet specific disease and treatment criteria as follows:
- TG A/A1/A2, TG B/B1/B2, C/C1, and TG E/E1: The subject must not be a candidate for potentially curative therapy or standard-of-care approved therapy.
- TG A2: The subjects must have confirmed diagnosis of PMF, PPV-MF, or PET-MF according to revised WHO 2016 criteria.
- TG D/D1: Subjects with newly diagnosed, treatment-naive AML who are unfit to tolerate standard intensive chemotherapy at study entry based on at least 1 of the following criteria:
? Age = 75 years old
? History of congestive heart failure (CHF) or documented ejection fraction (EF) = 50%
? Pulmonary disease with DLCO = 65% or FEVI = 65%, or dyspnea at rest or requiring oxygen
? Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy
- TG E/E1: The subjects in TG E must have previously received platinum-based therapy, but additional lines of therapies are allowed. The subjects in TG E1 must not have received more than 1 previous line of therapy for locally advanced or metastatic SCLC. The previous line of therapy must be a platinum-based therapy, and the subjects must have progressed on or after this treatment.
5. Willingness to undergo a pretreatment bone marrow biopsy or aspirate (AML/MDS/MF) during screening (may be waived with medical monitor approval). For subjects with solid malignancies, must have baseline archival tumor specimen available: a tumor block or approximately 15 slides from biopsy or resection of primary tumor or metastasis that are < 2 years old (specimens > 2 years old may be accepted with medical monitor approval).

Please refer to study protocol for further inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes

Exclusion Criteria

1. Receipt of anticancer medications, anticancer therapies, or investigational drugs within the following interval before the first administration of study drug (requirement may be waived with medical monitor approval):
a. < 5 half-lives or 14 days, whichever is longer, for any investigational agent
b. < 5 half-lives for all other anticancer medications
c. < 6 weeks for mitomycin-C or nitrosoureas
2. Any unresolved toxicity = Grade 2 from previous anticancer therapy except for stable chronic toxicities (= Grade 2) not expected to resolve.
3. All treatment groups: prior receipt of an LSD1 inhibitor therapy. Parts 3 and 4 TG E/E1: prior receipt of anti–programmed cell death-1, anti–programmed death ligand 1, or anti–PD-L2 antibody.
4. Any of the following laboratory results at screening without transfusions and hematopoietic growth factor support in solid tumors (no lower limits in AML and MDS, or in MF with medical monitor approval):
Absolute neutrophil count (× 109/L): < 1.5
Hemoglobin (g/dL): < 9.0
Platelet count (× 109/L): < 100
5. Laboratory and medical history parameters outside Protocol-defined range unless associated with primary malignancy or metastatic disease and with medical monitor approval:
a. Total bilirubin > 1.5 × institutional upper limit of normal (ULN) if no liver metastases or > 3 × ULN in the presence of liver metastases or presence of documented Gilbert syndrome (unconjugated hyperbilirubinemia).
b. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.0 × institutional ULN.
c. Creatinine clearance < 60 mL/min based on the institutional formula.

Please refers to study protocol for further exclusion criteria

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified