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

Completed

• Conditions: advanced malignaties; several types of severe cancer; 10024324; 10027655; 10029107

• Registration Number: NL-OMON48925
• Lead Sponsor: Incyte Biosciences UK Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 10

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: Newly diagnosed, treatment-naive AML, or MDS who are
unfit to tolerate standard intensive chemotherapy at study entry and who are
eligible to receive azacitidine as first-line therapy for the disease under
study.
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 diffusing capacity of the lungs for carbon monoxide*
65% or FEVI * 65%, or dyspnea at rest or requiring oxygen
* Any other comorbidity that the physician judges to be incompatible with
intensive chemotherapy
OR
Subjects with newly diagnosed, treatment-naïve, IPSS-R intermediate or higher
risk disease MDS who have at least 5% bone marrow blasts, who are unfit to
tolerate standard intensive chemotherapy at study entry and who are eligible to
receive azacitidine as first-line therapy for the disease under study.
The following treatments for prior lower risk MDS are acceptable:
Revlimid®, low-dose cytarabine, and growth factors.
* 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 monito

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
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>* Parts 1 and 2: Safety and tolerability as assessed by monitoring frequency,<br /><br>duration, and severity of adverse events (AEs) through physical examinations,<br /><br>by evaluating changes in vital signs and electrocardiograms (ECGs), and through<br /><br>clinical laboratory blood and urine sample evaluations.<br /><br>* Parts 3 and 4: Safety and tolerability as assessed by monitoring frequency,<br /><br>duration, and severity of AEs through physical examinations, by evaluating<br /><br>changes in vital signs and ECGs, and through clinical laboratory blood and<br /><br>urine sample evaluations in combinations therapies.</p><br>