A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

Official title

A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

Overview

This study is being conducted to evaluate the safety, tolerability, and dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a monotherapy or in combination with ruxolitinib in participants with myeloproliferative neoplasms.

Interventions

• Drug INCA033989
  INCA033989 will be administered at protocol defined dose.
• Drug Ruxolitinib
  Rux will be administered according to Prescribing Information/SmPC.

Primary outcome measures

• Number of participants with Dose Limiting Toxicities (DLTs) [Time frame: Up to 28 days]
• Number of participants with Treatment-emergent Adverse Events (TEAEs) [Time frame: Up to 3 years and 60 days]
• Number of participants with TEAEs leading to dose modification or discontinuation [Time frame: Up to 3 years and 60 days]

Secondary outcome measures (12)

• Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF [Time frame: Up to 3 years and 60 days]
• Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol [Time frame: Up to 3 years and 60 days]
• Participants with MF with symptomatic anemia: Anemia Response [Time frame: Up to 3 years and 60 days]
• Participants With ET: Response Rate [Time frame: Up to 3 years and 60 days]
• Participants With ET: Mean change from baseline of total symptom score (TSS) [Time frame: Up to 3 years and 60 days]
• Mean change in disease-related allele burden [Time frame: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: Cmax of INCA33989 [Time frame: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: Tmax of INCA033989 [Time frame: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: Cmin of INCA33989 [Time frame: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: AUC(0-t) of INCA33989 [Time frame: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: AUC 0-∞ of INCA33989 [Time frame: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: CL/F of INCA33989 [Time frame: Up to 3 years and 60 days]

Eligibility criteria

Inclusion criteria

• Life expectancy > 6 months.
• Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
• Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
• Participants with MF and ET as defined in the protocol.

Exclusion criteria

• Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
• Active invasive malignancy over the previous 2 years.
• Active HBV/HCV, HIV.
• History of clinically significant or uncontrolled cardiac disease.
• Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
• Laboratory values outside the Protocol-defined ranges.
• Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
• Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
• Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 5 centers

• National Cancer Center Hospital East — Chiba-ken
• Kagoshima University Hospital — Kagoshima
• Osaka Metropolitan University Hospital — Osaka
• Nippon Medical School Hospital — Tokyo
• Mie University Hospital — Tsu

Australia · 4 centers

• Royal Brisbane and Women'S Hospital — Herston
• Royal Adelaide Hospital — Adelaide
• Peter Maccallum Cancer Centre — Melbourne
• The Alfred Hospital — Melbourne

France · 4 centers

• Institut Bergonie — Bordeaux
• Chu Nimes — Nîmes
• Hospital Saint Louis — Paris
• Institut Gustave Roussy — Villejuif

Denmark · 3 centers

• Odense University Hospital — Odense C
• Sjaellands Universitetshospital — Roskilde
• Vejle Hospital — Vejle

Germany · 3 centers

• University Medical Center Rwth Aachen — Aachen
• Universitatsklinikum Halle (Saale) — Halle
• Universitätsklinikum Ulm — Ulm

Italy · 3 centers

• Aou Policlinico S. Orsola-Malpighi — Bologna
• Azienda Ospedaliero-Universitaria Careggi (Aouc) — Florence
• Fondazione Irccs Ca Granda Ospedale Maggiore — Milan

United Kingdom · 3 centers

• Guys and St Thomas Nhs Foundation Trust — London
• The Christie Nhs Foundation Trust Uk — Manchester
• University of Oxford — Oxford

Canada · 2 centers

• Princess Margaret Cancer Center — Toronto
• Hopital Maisonneuve-Rosemont, Montreal, Qc — Montreal

Spain · 2 centers

• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitari I Politecnic La Fe — Valencia

Identifiers

NCT: NCT05936359 · INCA 33989-101 · 2022-502514-86-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗