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RecruitingLast updated: 4 January 2024

LIMBER: This study aims to determine the safety, tolerability and recommended dosage level of a new drug when it is given alone, or in combination with targeted therapy, in people with myeloproliferative neoplasmsA Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

Clinical summary

Summary

This study has three parts, and will evaluate a new drug (called INCA033989) alone, or in combination with targeted therapy (called ruxolitinib). The study will recruit:

  • People with myelofibrosis (MF).
  • People with essential thrombocythemia (ET).
  • People with myelofibrosis exhibiting suboptimal response (MF SubOptR).

In the Dose Escalation Part (Part 1a), people with MF and ET will receive INCA033989 as monotherapy, which will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]).

People with MF SubOptR will receive INCA033989, which will be administered at a protocol defined starting regimen in 28-day cycles and will allow for evaluation of INCA033989 in combination with targeted therapy (called ruxolitinib) to identify the MTD and/or RDE[s].

In the Dose Expansion Part (Part 1b), participants with MF and ET will receive INCA033989 as monotherapy at the RDE[s] identified during Part 1a. 

Participants with MF-SubOpt R will receive INCA033989 as an add-on therapy in combination with ruxoclitinib at the RDE[s] identified during Part 1a.

In the Dose Expansion Part (Part 1c), INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with ruxolitinib. Participants with MF will enroll int his group. THe participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks. 

Conditions

This trial is treating patients with Myeloproliferative Neoplasms

Cancer

Blood Cancers Haematological

Age

People18+

Phase

I

Trial Acronym

LIMBER

More information

Trial Identifiers

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Trial sponsor

Incyte Corporation

Scientific Title

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

Eligibility

Inclusion

  • 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

  • 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 or GM-CSF, romiplostim, or eltrombopag 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.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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