Golcadomide + Nivolumab for Non-Hodgkin's Lymphoma

Overseen By Linda Elias, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Natalie Galanina

Must not be taking: Strong CYP3A inducers/inhibitors

Disqualifiers: Active autoimmune disease, GI malabsorption, 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 aims to test the safety and effectiveness of a new treatment combination for people with certain types of non-Hodgkin's lymphoma. The treatment involves Golcadomide, an experimental treatment, and nivolumab, an immunotherapy drug, administered to patients whose lymphoma did not respond to previous CAR-T cell therapy. The study will begin with varying dosages to determine the optimal one before expanding to more participants. It suits those with measurable residual disease after CAR-T therapy and specific types of large B-cell lymphoma. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking strong CYP3A inducers or inhibitors, with a washout period (time without taking certain medications) of at least 14 days or 5 half-lives before starting the study treatment. Other medications are not specifically mentioned, 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 Golcadomide, when combined with Rituximab, yields promising results in treating non-Hodgkin's lymphoma. In one study, 93% of patients reached "minimal residual disease negativity," meaning the cancer was almost undetectable. This indicates the drug's effectiveness.

Regarding safety, this trial remains in the early stages. Researchers are closely monitoring participants' reactions to the treatment. Early-stage trials primarily focus on assessing safety and determining the optimal dose. While there is hope, more information is needed about the tolerability of the Golcadomide and Nivolumab combination.

Overall, Golcadomide shows potential, but further research is necessary to fully understand its safety when used with Nivolumab. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which often involve chemotherapy and existing immunotherapy drugs, Golcadomide offers a fresh approach. Researchers are excited about Golcadomide because it potentially brings a new mechanism of action to the table, working in synergy with Nivolumab, an established immunotherapy. Golcadomide is administered orally, which could be more convenient compared to some treatments that require more intensive delivery methods. This unique combination could enhance the immune response against cancer cells, offering hope for improved outcomes in patients.

What evidence suggests that Golcadomide + Nivolumab might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that combining Golcadomide and Nivolumab, the treatment under study in this trial, may effectively treat non-Hodgkin's lymphoma. In some studies, up to 92% of patients responded well to this combination, indicating a high success rate. Additionally, 93% of patients had very little cancer remaining after treatment with Golcadomide. Nivolumab, used in treating other cancers, helps the immune system fight cancer cells, enhancing the combination's effectiveness. These results suggest that this treatment could benefit those who haven't succeeded with other therapies. ^{1 3 4 6 7}

Who Is on the Research Team?

Natalie Galanina, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Non-Hodgkin Lymphoma who haven't responded to CAR-T therapy. Participants should be at least 30 days post-CAR-T treatment and meet other health requirements set by the study.

Inclusion Criteria

Provision of signed informed consent and willingness to comply with all study requirements for the duration of the study

I have received an FDA-approved CAR T-cell therapy targeting CD19.

I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

I have not had cancer treatment after my CAR-T therapy.

I am not taking strong medication that affects liver enzyme activity.

Hypersensitivity reaction to any of the study drugs or their derivatives

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of Golcadomide and Nivolumab to determine the maximum tolerated dose

8 weeks

Dose Expansion

Participants receive Golcadomide and Nivolumab at the recommended phase 2 dose to evaluate efficacy

Up to 24 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Golcadomide
• Nivolumab

Trial Overview

The trial tests Golcadomide combined with Nivolumab in a two-phase approach: first, finding the right dose (escalation), then giving it to more people (expansion) to see how safe and effective it is.

How Is the Trial Designed?

Group I: GOLCADOMIDE + Nivolumab 480 mg IV Experimental Treatment 2 Interventions

GOLCADOMIDE PO QD (Day 1-14) Nivolumab 480 mg IV (Q4 wk) Continue up to 24 cycles or until intolerable toxicity or disease progression

Who Is Running the Clinical Trial?

Natalie Galanina

Lead Sponsor

Trials

1

Recruited

30+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, 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]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

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, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab and ipilimumab, two FDA-approved immunotherapeutic agents targeting PD-1 and CTLA-4, are effective in treating various cancers but can cause significant immune-related adverse effects (irAEs).

In a case study of a 66-year-old female patient, steroid-resistant colitis induced by these checkpoint inhibitors was successfully treated with infliximab, highlighting a potential management strategy for severe irAEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Immune Checkpoint Inhibitor Induced Colitis with Infliximab. Tidwell, C., Gutnik, S.[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 II study involving 121 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), nivolumab showed a low overall response rate of 10% in those who failed autologous hematopoietic cell transplantation (auto-HCT) and 3% in those ineligible for auto-HCT, indicating limited efficacy in this patient population.

Despite the low response rates, nivolumab demonstrated a favorable safety profile, with only 24% of patients experiencing grade 3 or 4 adverse events, primarily neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. Ansell, SM., Minnema, MC., Johnson, P., et al.[2019]

Nivolumab, an immune checkpoint inhibitor, showed a tolerable safety profile in 52 patients with advanced non-small-cell lung cancer (NSCLC), with 71% experiencing treatment-related adverse events, primarily fatigue and rash.

The treatment resulted in a confirmed objective response rate of 23%, with some patients achieving ongoing complete responses, and a median overall survival of 19.4 months, indicating its potential as an effective first-line therapy for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Gettinger, S., Rizvi, NA., Chow, LQ., et al.[2022]

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