Nivolumab + Axatilimab for Hodgkin's Lymphoma

(NAHL Trial)

Recruiting at 1 trial location

Overseen By Catherine Cromar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must be taking: Anti-PD-1/PD-L1 therapy

Must not be taking: CSF-1/CSF-1R/IL-34 agents

Disqualifiers: Autoimmune disease, Pulmonary disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: 12 months

9 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to study the combination of nivolumab and axatilimab in patients with relapsed/refractory classical Hodgkin Lymphoma. This study will mainly look at if the combination works as expected.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are prohibited as described in the study protocol. There is a washout period (time without taking certain medications) of at least five half-lives or as clinically indicated before starting the trial treatment. You can continue taking Nivolumab if you are already on it.

What data supports the effectiveness of the drug Nivolumab + Axatilimab for treating Hodgkin's Lymphoma?

Nivolumab has shown effectiveness in treating relapsed or refractory classic Hodgkin's lymphoma by enhancing the immune system's response to cancer cells, leading to reduced tumor growth. It has been approved by the FDA for use in various cancers, including Hodgkin's lymphoma, and has demonstrated frequent and durable responses in clinical trials. ^{1 2 3 4 5}

Is the combination of Nivolumab and Axatilimab generally safe for humans?

Nivolumab has been studied in various cancers, including Hodgkin's lymphoma, and generally has a manageable safety profile, though it can cause immune-related side effects like pneumonitis (lung inflammation). Safety data for Axatilimab specifically is not provided, but Nivolumab's safety in different conditions suggests it is generally safe with careful monitoring. ^{3 4 6 7 8}

What makes the drug combination of Nivolumab and Axatilimab unique for treating Hodgkin's Lymphoma?

The combination of Nivolumab and Axatilimab is unique because Nivolumab is a monoclonal antibody that enhances the immune system's ability to fight cancer by blocking proteins that prevent immune cells from attacking cancer cells, and Axatilimab may offer additional benefits, although its specific role in this combination is not detailed in the available research. ^{1 2 3 4 9}

Research Team

Harsh Shah, MD

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

Adults with relapsed or refractory Classical Hodgkin Lymphoma who have tried anti-PD-1/anti-PDL-L1 therapy like nivolumab can join. They need measurable disease, good organ function, and no recent transplants or immunosuppressive treatments. Pregnant women can't participate, and effective contraception is required.

Inclusion Criteria

Subject must have at least one measurable area of disease (greater than 1.5 cm longest transverse diameter (LDi) by Lugano Criteria

Subjects with a prior autologous transplant are eligible

I have recovered from side effects of previous cancer treatments.

Exclusion Criteria

I have never had PML, HLH, CNS vasculitis, uncontrolled seizures, or neurodegenerative disease.

I have brain metastases or cranial epidural disease.

I do not have any severe illnesses that are not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

A dose de-escalation design will be used to determine the recommended phase 2 dose, ensuring safety and tolerability

8 weeks

2 visits (in-person)

Treatment

Participants receive Axatilimab 3mg/kg and Nivolumab 480mg every 4 weeks, continued until progression/toxicity or a maximum of 12 months

12 months

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

Treatment Details

Interventions

• Axatilimab
• Nivolumab

Trial Overview The trial tests a combination of two drugs: Nivolumab and Axatilimab in patients whose Hodgkin Lymphoma didn't respond to previous treatments. It aims to see if this drug duo works better together for these patients.

Participant Groups

Group I: Treatment: All Patients Experimental Treatment 2 Interventions

Nivolumab 480 mg IV Q4 weeks Axatilimab (SNDX 6532) dose (3mg/kg IV) Q4 weeks. If DLT criteria are met, Axatilimab dosing will be reduced to 2mg/kg IV Q4W for the remainder of patients on the study. The combination will be continued until progression/toxicity up to a maximum of 12 cycles.

Axatilimab is already approved in United States for the following indications:

Approved in United States as Axatilimab for:

• Chronic Graft-Versus-Host Disease

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Incyte Corporation

Industry 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

Findings from Research

Nivolumab, an antibody that enhances T-cell responses against tumors, was effective in achieving complete remission in a 65-year-old woman with refractory Hodgkin's lymphoma, despite her experiencing serious side effects like interstitial pneumonitis and cardiac hypokinesis after treatment.

The patient's cardiac function improved significantly after discontinuing Nivolumab and receiving appropriate management, highlighting the importance of monitoring and managing immune-related adverse events in patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-induced pneumonitis and cardiopathy in a patient with relapsed Hodgkin's lymphoma. Bonhomme-Faivre, L., Guarino, V., Misra, SC.[2023]

In a study involving 51 patients with newly diagnosed advanced-stage classic Hodgkin lymphoma, nivolumab followed by a combination therapy (N-AVD) showed an impressive objective response rate of 84%, with 67% of patients achieving complete remission.

The treatment was generally well-tolerated, with 59% of patients experiencing grade 3 to 4 treatment-related adverse events, but most were manageable, and the 9-month modified progression-free survival rate was 92%, indicating strong efficacy and safety for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. Ramchandren, R., Domingo-Domènech, E., Rueda, A., et al.[2021]

Nivolumab, an immune checkpoint inhibitor targeting PD-1, has shown effectiveness in treating various cancers, including Hodgkin lymphoma, as evidenced by a partial response in a 75-year-old patient after multiple treatments.

The case highlights a potential risk where discontinuation of nivolumab led to the emergence and progression of new malignancies, suggesting that while ICIs can be effective, they may also uncover or allow the growth of other cancers in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two primary cancers appeared after discontinuation of nivolumab in the course of treating Hodgkin lymphoma: a case report. Potluri, LB., Nanjareddy, S., Al Sbihi, A., et al.[2023]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

In a phase II clinical trial involving 17 patients with relapsed or refractory classical Hodgkin lymphoma, the combination of nivolumab and ibrutinib resulted in a complete response rate of 29.4%, which did not meet the target of 50%.

Despite not achieving the primary efficacy endpoint, the treatment showed promising durability of responses, with a median progression-free survival of 17.3 months, suggesting that further studies on this combination therapy are needed, especially for patients who have previously progressed on checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma. Hanel, W., Shindiapina, P., Bond, DA., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

In a case series of 16 people living with HIV who received nivolumab, 14% achieved complete responses, particularly notable in those with Hodgkin lymphoma, indicating potential efficacy similar to that seen in HIV-uninfected patients.

The study found that 40% of patients experienced immune-related adverse effects, with 27% developing pneumonitis, suggesting that while nivolumab can be effective, monitoring for side effects is crucial, especially in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Treatment for Cancers in the HIV-infected Population. Chang, E., Sabichi, AL., Kramer, JR., et al.[2020]

In a phase 2 study involving 80 patients with relapsed classical Hodgkin's lymphoma, nivolumab demonstrated a high objective response rate of 66.3%, indicating its efficacy as a treatment option after failure of both autologous stem-cell transplantation and brentuximab vedotin.

Nivolumab was found to have an acceptable safety profile, with common side effects including fatigue and infusion-related reactions, and no treatment-related deaths reported, suggesting it is a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Younes, A., Santoro, A., Shipp, M., et al.[2022]

Nivolumab shows a favorable safety profile and a 65% objective response rate in patients with classical Hodgkin lymphoma, indicating its efficacy as a treatment option.

The study recommends a dosing regimen of 240 mg every 2 weeks, as it provides similar drug exposure to the previously used 3 mg/kg every 2 weeks, while maintaining safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure - Safety Analyses of Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma. Wang, X., Ludwig, EA., Passarell, J., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Nivolumab-induced pneumonitis and cardiopathy in a patient with relapsed Hodgkin's lymphoma. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. [2021]

3. China pubmed.ncbi.nlm.nih.gov

Two primary cancers appeared after discontinuation of nivolumab in the course of treating Hodgkin lymphoma: a case report. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Nivolumab Treatment for Cancers in the HIV-infected Population. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure - Safety Analyses of Nivolumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma. [2020]