Copanlisib + Nivolumab for Lymphoma

Not currently recruiting at 3 trial locations

Overseen By Alexey Danilov, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inhibitors, Corticosteroids

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Compensation: Varies

Number of Visits: 6

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, copanlisib and nivolumab, to determine the optimal dose and assess their effectiveness against certain types of lymphoma. Copanlisib blocks important enzymes to stop tumor growth, while nivolumab, an immunotherapy, helps the immune system attack cancer cells. Ideal participants have a specific type of transformed lymphoma and have not succeeded with other treatments. 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 combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use strong CYP3A4 inhibitors or inducers within 2 weeks before starting the study therapy, and you should not be on chronic corticosteroids exceeding 15 mg of prednisone per day.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the combination of copanlisib and nivolumab is generally well tolerated by patients with various types of cancer. Studies have found that the side effects of this treatment are manageable. In patients with advanced solid tumors, this combination was well tolerated and showed promising results.

Other research indicates that patients with certain types of lymphoma also tolerated the combination well, suggesting it could be a safe option for those considering this treatment. Although this trial remains in its early stages, current evidence provides a positive outlook on the safety of using copanlisib and nivolumab together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Copanlisib and Nivolumab for treating lymphoma because it brings a fresh approach to tackling the disease. Unlike traditional chemotherapy, which broadly attacks rapidly dividing cells, Copanlisib is a targeted therapy that inhibits a specific protein called PI3K, which plays a crucial role in cancer cell growth. Nivolumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Together, these drugs offer a dual attack strategy: one interferes with cancer cell growth, and the other boosts the body's natural defenses, potentially leading to more effective and personalized treatment outcomes.

What evidence suggests that copanlisib and nivolumab might be an effective treatment for lymphoma?

Research has shown that using copanlisib and nivolumab together, as studied in this trial, may help treat certain cancers. Studies have found that this combination has manageable side effects and works well for patients with transformed non-Hodgkin lymphoma. Copanlisib inhibits proteins that promote cancer cell growth, while nivolumab boosts the immune system to fight cancer. Early results also suggest that this combination might be effective for other cancers, such as colorectal cancer. Overall, these treatments have demonstrated effects against tumors that could benefit patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Alexey V Danilov

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with Richter's transformation or transformed indolent non-Hodgkin lymphoma who've had at least one prior treatment. Participants must have measurable disease, acceptable organ function, and agree to contraception if applicable. Exclusions include pregnancy, uncontrolled health conditions like hypertension or bleeding disorders, recent major surgery, live vaccines, certain heart issues, and previous treatments with similar drugs.

Inclusion Criteria

I have lymphoma, have tried at least one treatment without success, and am not planning or eligible for a stem cell transplant.

I have had at least 2 treatments for my Richter's Syndrome or CLL.

Your AST and ALT levels are lower than 2.5 times the normal limit at the medical facility where you are being treated.

Exclusion Criteria

I haven't had cancer treatments like antibodies, radiation, or chemotherapy recently.

My cancer has spread to my brain or spinal cord.

I have had a bone marrow or organ transplant from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive copanlisib IV on days 1, 8, and 15 and nivolumab IV on days 1 and 15, repeating every 28 days for up to 12 cycles

48 weeks

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

12 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Copanlisib
• Nivolumab

Trial Overview The trial tests the combination of copanlisib (blocks enzymes for cell growth) and nivolumab (boosts immune system against cancer). It aims to find the best dose and see how well these drugs work together in treating specific types of lymphoma by stopping tumor growth and helping the body attack cancer cells.

How Is the Trial Designed?

Group I: Treatment (copanlisib and nivolumab) Experimental Treatment 2 Interventions

Patients receive copanlisib IV over 60 minutes on days 1, 8, and 15 and nivolumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 311 patients treated with nivolumab or pembrolizumab for advanced melanoma or lung cancer, 37.3% experienced immune-related adverse events, which were linked to improved overall survival rates.

Patients who had immune-related adverse events showed a significantly higher overall response rate (53.9%) compared to those without such events (12.9%), suggesting that these adverse effects may indicate better treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non-small-cell lung cancer: a real-life retrospective study. Dupont, R., Bérard, E., Puisset, F., et al.[2021]

Nivolumab and pembrolizumab, both anti-PD-1 therapies, show promising efficacy in treating relapsed or refractory lymphoma, with an overall response rate of 58% and a 6-month overall survival rate of 96% across 10 studies involving 718 patients.

While both treatments have tolerable adverse effects, pembrolizumab is associated with fewer instances of fatigue and rash compared to nivolumab, and patients with Hodgkin lymphoma respond better to treatment than those with non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Anti-PD-1 Monoclonal Antibodies in Patients With Relapsed or Refractory Lymphoma: A Meta-Analysis of Prospective Clinic Trails. Zhou, H., Fu, X., Li, Q., et al.[2020]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

The phase III CHRONOS-3 trial demonstrated that adding copanlisib, a pan-PI3K inhibitor, to standard rituximab significantly benefits patients with relapsed indolent non-Hodgkin lymphoma.

This combination therapy was found to be safe and reduced the risk of disease progression or death by nearly 50% compared to the placebo plus rituximab group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NHL Progression Risk Cut with Copanlisib-Rituximab Combo. [2021]

Copanlisib is effective in treating relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), with an overall response rate of 57% and a complete response rate of 13% based on a meta-analysis of 652 patients across 8 studies.

Combination therapy with copanlisib and rituximab showed significantly higher efficacy compared to copanlisib alone, with complete response rates of 34% versus 6%, while treatment-related adverse events were manageable, with common side effects including hyperglycemia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of copanlisib in relapsed/refractory B-cell non-Hodgkin lymphoma: A meta-analysis of prospective clinical trials. Wang, J., Zhou, H., Mu, M., et al.[2022]

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]

In a phase 1b trial involving 137 patients with relapsed/refractory lymphoid malignancies, the combination of nivolumab with ipilimumab or lirilumab showed significant activity in classical Hodgkin lymphoma, with overall response rates of 74% and 76%, respectively.

However, the combination therapies did not demonstrate a meaningful improvement in efficacy compared to single-agent nivolumab, and the combination with ipilimumab resulted in higher rates of severe treatment-related adverse events (29%) compared to lirilumab (15%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies. Armand, P., Lesokhin, A., Borrello, I., et al.[2021]

Checkpoint inhibitors like nivolumab and pembrolizumab are effective treatment options for patients with relapsed or refractory classic Hodgkin lymphoma, particularly for those who cannot undergo autologous stem-cell transplantation due to health issues.

These treatments not only improve overall survival rates but also have a manageable side effect profile, making them a safer alternative for patients with comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibition Therapy in Transplant-Ineligible Relapsed or Refractory Classic Hodgkin Lymphoma. Al-Hadidi, SA., Lee, HJ.[2022]

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]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

Monoclonal antibodies like nivolumab and pembrolizumab, which target PD-1, have shown a survival benefit and better tolerability compared to standard second-line chemotherapy in non-small cell lung cancer, as demonstrated in three phase III trials.

Patients receiving PD-1 inhibitors may experience unique immune-related adverse events that require early recognition and a multidisciplinary management approach, highlighting the need for ongoing education among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. O'Kane, GM., Labbé, C., Doherty, MK., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11907410/

A Phase Ib Study in Patients with Advanced Solid Tumors - PMC The combination of copanlisib and nivolumab was well tolerated and showed antitumor effects in patients with advanced solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03502733

Testing the Combination of Copanlisib, Nivolumab and ... Copanlisib stops tumors from growing by blocking proteins that are known to be important for tumor cell growth. Immunotherapy with monoclonal antibodies, such ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40605718/

Safety and efficacyof the combination of copanlisib and ... Overall, treatment with copanlisib and nivolumab demonstrated manageable toxicity and promising clinical efficacy in tNHL patients.

4. onclive.com onclive.com/view/early-data-with-copanlisib-nivolumab-combo-support-further-exploration-in-mss-crc

Early Data With Copanlisib/Nivolumab Combo Support ... Eric S. Christenson, MD, discusses the potential benefit of copanlisib plus nivolumab in PIK3CA-mutant microsatellite stable colorectal cancer.

5. everyone.org everyone.org/explore/compare?id1=21&id2=102

Opdivo (Nivolumab) vs Aliqopa (copanlisib) Clinical trials have demonstrated that Nivolumab can induce a response in a significant proportion of these patients. The efficacy of Nivolumab was evaluated in ...

6. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/3/444/754187/Safety-and-Efficacy-of-Copanlisib-in-Combination

Safety and Efficacy of Copanlisib in Combination with ... The combination of copanlisib and nivolumab was well tolerated and showed antitumor effects in patients with advanced solid tumors. The number of circulating ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39927513/

A Phase Ib Study in Patients with Advanced Solid Tumors The combination of copanlisib and nivolumab was well tolerated and showed antitumor effects in patients with advanced solid tumors.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03484819?term=AREA%5BInterventionSearch%5D(BAY-80-6946)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=5

Copanlisib Hydrochloride and Nivolumab in Treating ... This phase II trial studies how well copanlisib hydrochloride and nivolumab work in treating patients with diffuse large B-cell lymphoma or primary ...