INCB040093 + Itacitinib for B-Cell Lymphoma

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Incyte Corporation

Must not be taking: Anticancer medications

Disqualifiers: Brain metastases, CNS lymphoma, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with B-cell lymphoma, a cancer affecting certain white blood cells. Researchers aim to determine how well the drugs INCB040093 and itacitinib work alone and together against this condition. The trial seeks participants who have tried at least one other cancer treatment without success and are not eligible for curative therapies like a stem cell transplant. For those dealing with B-cell lymphoma and unsuccessful previous treatments, this trial might be suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new potential therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any approved anticancer medications at least 21 days before starting the study drug, except for low-dose steroids (10 mg prednisone daily or equivalent). If you are on other medications, the protocol does not specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of INCB040093 and itacitinib is generally well-tolerated. In earlier studies, this treatment appeared promising for patients with certain types of B-cell lymphomas, a cancer affecting white blood cells. Patients experienced fewer severe side effects, such as high liver enzyme levels, when using the combination, suggesting it might be safer than using INCB040093 alone.

For INCB040093 alone, previous research indicates it has been safe enough for further testing. Studies in animals like rats and dogs showed an acceptable safety margin, meaning INCB040093 did not cause serious harm at effective doses.

These findings offer some reassurance about the treatment’s safety in humans, but this study remains in its early phase. Researchers are still determining the best dose to use without causing too many side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about INCB040093 and itacitinib for B-cell lymphoma because these treatments offer a novel approach compared to current options like chemotherapy or monoclonal antibodies. Unlike standard treatments that broadly attack cancer cells, INCB040093 is a PI3K delta inhibitor that specifically targets pathways crucial for the survival of lymphoma cells, potentially leading to fewer side effects. Itacitinib, on the other hand, is a JAK1 inhibitor, working by interfering with the signaling processes that help cancer cells grow and evade the immune system. Together, these drugs are designed to more precisely attack cancer, which could mean more effective results with potentially better tolerability for patients.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

Research has shown that INCB040093, a type of medication, holds promise in treating B-cell lymphomas, a kind of blood cancer. In earlier studies, 63% of patients with follicular lymphoma responded well to this treatment. In this trial, some participants will receive INCB040093 alone, while others will receive it combined with another medication called itacitinib. This combination works especially well for classic Hodgkin lymphoma and tends to have fewer serious side effects, such as liver issues, compared to other treatments. Both INCB040093 alone and with itacitinib have effectively slowed down or stopped tumor growth in these cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Peter Langmuir, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

Adults with B-cell lymphoma or other B-cell malignancies who have tried at least one treatment and aren't eligible for curative therapies like stem cell transplants. They should be in a condition to live at least 12 more weeks, not have brain involvement by cancer, and can't be recovering from recent cancer treatments or active infections.

Inclusion Criteria

Indolent / aggressive B-cell (NHL) Non- Hodgkin's Lymphoma: EXCLUDING: Burkitt lymphoma and precursor B-lymphoblastic leukemia/lymphoma INCLUDING: any non-Hodgkin's B-cell malignancy such as CLL and rare non-Hodgkin's B-cell subtypes such as Hairy Cell Leukemia, Waldenstrom macroglobulinemia, Mantle cell lymphoma, transformed NHL histologies, etc.

Hodgkin's lymphoma

Life expectancy of 12 weeks or longer.

Exclusion Criteria

Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study drug.

Received any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) prior to receiving their first dose of study drug (42 days for nitrosoureas) EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent).

Has any unresolved toxicity ≥ Grade 2 from previous anticancer therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 is a dose escalation phase to determine the maximum tolerated dose (MTD) of INCB040093, a PI3Kδ inhibitor, or a tolerated, pharmacologically active dose

8 weeks

Combination Evaluation

Part 2 will evaluate the combination of INCB040093 and itacitinib (INCB039110), a JAK1 inhibitor, to determine the MTD of the combination or a tolerated dose that produces substantial pharmacologic inhibition of both targets

8 weeks

Further Evaluation

Part 3 will further evaluate the chosen doses of INCB040093 alone and in combination with itacitinib (INCB039110) in subjects with relapsed/refractory B-cell malignancies

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• INCB040093
• itacitinib

Trial Overview The trial is testing INCB040093 alone and combined with itacitinib on people with B-cell cancers. It has three parts: finding the safest dose of INCB040093, then its combination with itacitinib, and finally evaluating these doses in patients whose disease returned after treatment.

How Is the Trial Designed?

Group I: INCB040093 in combination with itacitinib (INCB039110) Experimental Treatment 1 Intervention

Group II: INCB040093 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29695516/

Phase 1 study of the PI3Kδ inhibitor INCB040093 ± JAK1 ... This phase 1 dose-escalation/expansion study assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of INCB040093, a selective ...

2. ashpublications.org ashpublications.org/blood/article/132/3/293/39253/Phase-1-study-of-the-PI3K-inhibitor-INCB040093

Phase 1 study of the PI3Kδ inhibitor INCB040093 ± JAK1 ... INCB040093 was active across the B-cell lymphomas; 63% of patients (5/8) with follicular lymphoma responded to monotherapy. Adding itacitinib ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0022356524261322

INCB040093 Is a Novel PI3Kδ Inhibitor for the Treatment of ... INCB040093 is a novel PI3Kδ small-molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies.

4. trial.medpath.com trial.medpath.com/clinical-trial/b771f2f0a0d151d7/safety-tolerability-study-INCB040093-B-cell-malignancies

Study of INCB040093 in Subjects With Previously Treated B ... The study will be conducted in three parts. Part 1 is a dose escalation phase to determine the maximum tolerated dose (MTD) of INCB040093, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497120320632

Phase 1 study of the PI3Kδ inhibitor INCB040093 ± JAK1 ... INCB040093 was active across the B-cell lymphomas; 63% of patients (5/8) with follicular lymphoma responded to monotherapy. Adding itacitinib ...

6. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.8558

A phase 1 study of INCB040093, a PI3Kδ inhibitor, alone or ... Safety, efficacy, and pharmacodynamics were evaluated. Data from the r/r cHL pts are reported herein. Results: A total of 17 pts with r/r cHL ...