Nivolumab + Axatilimab for Hodgkin's Lymphoma

(NAHL Trial)

Recruiting at 1 trial location

Overseen By Rachel Kingsford

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two treatments, nivolumab (an immunotherapy drug) and axatilimab (an experimental treatment), can benefit patients with Hodgkin's Lymphoma that has recurred or not responded to other treatments. The study aims to determine if this combination effectively controls the disease. It seeks participants who have tried at least one other therapy without success, have been on anti-PD-1 or anti-PDL-1 treatments, and still have measurable disease. Those with frequent relapses of Hodgkin's Lymphoma and unsuccessful previous treatments may find this an opportunity. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that patients generally tolerate the combination of nivolumab and axatilimab well. In a study with 19 patients who had a type of Hodgkin lymphoma that recurred or resisted treatment, this combination proved safe. Patients managed the treatment well, with 39% responding positively.

When combined with chemotherapy for Hodgkin lymphoma, nivolumab has demonstrated a high survival rate of 92%. It also tends to cause fewer long-term side effects compared to some other treatments, indicating that nivolumab is relatively safe and manageable.

These findings suggest that the combination of nivolumab and axatilimab is likely safe for most people, although individual experiences may differ. Prospective participants should discuss these findings with their doctor to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Axatilimab for treating Hodgkin's Lymphoma because it offers a new approach compared to traditional therapies. Nivolumab is an immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells more effectively. Axatilimab targets and inhibits a different pathway, potentially reducing inflammation that contributes to the progression of the disease. Unlike conventional treatments, which might focus solely on chemotherapy or radiation, this dual approach harnesses the body's own defenses while also calming harmful inflammation, offering hope for a more effective and potentially less toxic treatment option.

What evidence suggests that the combination of nivolumab and axatilimab could be effective for Hodgkin's Lymphoma?

Research has shown that nivolumab effectively treats relapsed or refractory classical Hodgkin's lymphoma by enhancing the immune system's ability to fight cancer cells. Studies have reported impressive results, with one showing a 92% survival rate when nivolumab is combined with chemotherapy. In this trial, all participants will receive a combination of nivolumab and axatilimab. Although axatilimab is a newer drug and not as extensively studied, it is believed to complement nivolumab by supporting the immune system differently. Together, nivolumab and axatilimab offer hope for better outcomes in patients with this type of lymphoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Harsh Shah, MD

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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]

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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05723055

Evaluating Combination of Nivolumab and Axatilimab in ... The goal of this clinical trial is to study the combination of nivolumab and axatilimab in patients with relapsed/refractory classical Hodgkin Lymphoma.

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/hodgkin-lymphoma-nivolumab-avd-first-line

Nivolumab and AVD the New Standard in Hodgkin ... The 2-year progression-free survival rate of 88% among those in this age group treated with nivolumab–AVD “is probably the best ever reported,” ...

3. oncology-central.com oncology-central.com/nivolumab-improves-survival-and-reduces-long-term-side-effects-for-advanced-hodgkin-lymphoma-patients-2/

Nivolumab plus chemotherapy yields 92% survival rate for ... Advanced Hodgkin lymphoma patients who received chemotherapy alongside Opdivo (nivolumab) had a 92% survival rate and fewer side effects.

4. withpower.com withpower.com/trial/nivolumab-axatilimab-for-hodgkins-lymphoma-6ba68

Nivolumab + Axatilimab for 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, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39413375/

Nivolumab+AVD in Advanced-Stage Classic Hodgkin's ... Conclusions: N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10727015/

The optimal management of relapsed and refractory ... A phase 1/2 trial in 19 evaluable patients with relapsed/refractory cHL after prior CPI therapy was well tolerated and demonstrated an ORR of 39 ...

7. scientificarchives.com scientificarchives.com/article/immunotherapy-in-the-management-of-hodgkin-lymphoma-time-for-immunotherapy-for-all

Immunotherapy in the Management of Hodgkin Lymphoma CMR rate after single-agent pembrolizumab was 42% in patients with limited-stage, unfavorable disease, and increased to 100% after two additional cycles of AVD.