Copanlisib + Nivolumab for Lymphoma

No longer recruiting at 18 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Pi3 kinase inhibitors, Anti-PD-1

Disqualifiers: High grade B-cell lymphoma, 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: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining copanlisib and nivolumab for people with certain types of lymphoma (a type of blood cancer) that have returned or resisted previous treatments. Copanlisib aims to stop cancer cells from growing, while nivolumab, an immunotherapy drug, helps the immune system attack the cancer. Individuals with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma that hasn't improved with standard treatments might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you must stop taking your current medications, but you cannot use certain drugs that interact with copanlisib, like strong CYP3A4 inhibitors or inducers, from 14 days before joining the study. It's important to discuss your current medications with the trial team to ensure there are no interactions.

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

Research has shown that copanlisib hydrochloride is generally well-tolerated. In patients with relapsed or hard-to-treat B-cell non-Hodgkin lymphoma, common side effects included high blood sugar, high blood pressure, and diarrhea. These side effects were manageable, indicating the treatment's safety.

Studies have found nivolumab to be safe and effective for certain lymphomas. In one study, nivolumab reduced or eliminated tumors in some patients. Long-term data also supports its safety, demonstrating effectiveness over several years.

Both treatments have shown promise in earlier studies and are already used for other conditions, suggesting confidence in their safety. However, anyone considering joining a trial should discuss possible side effects with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using copanlisib and nivolumab for treating lymphoma because these drugs combine different mechanisms to tackle cancer. Copanlisib is a PI3K inhibitor, which means it blocks signals that tell cancer cells to grow, making it a novel addition compared to traditional chemotherapy. Nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Together, these drugs offer a promising new approach by pairing a targeted attack on cancer cell growth with an immune system boost, potentially leading to better outcomes than existing treatments like chemotherapy or single-agent therapies.

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

Research has shown that copanlisib hydrochloride shows promise in treating certain types of lymphoma, with over half of patients with follicular lymphoma responding to the treatment. Meanwhile, nivolumab has effectively helped people with various lymphomas live longer, with some studies showing a 92% survival rate in advanced Hodgkin lymphoma. This trial will evaluate the combination of copanlisib and nivolumab, which might be more effective against diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma. Early findings suggest that this combination could outperform current standard treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

Nabila N. Bennani

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with certain types of B-cell lymphoma that have not responded to or returned after treatment. Participants must have a specific level of blood counts, organ function, and be able to perform daily activities with minimal assistance. Pregnant women, those with recent other cancers or major treatments, active infections or severe diseases are excluded.

Inclusion Criteria

Platelet count >= 100,000/mm^3

Hemoglobin > 9.0 g/dL

I am a woman who can still have children, not sterilized, and not in menopause.

Exclusion Criteria

I have recovered from side effects of previous treatments, except for hair loss.

I have been checked for serious gut issues before joining the study.

I do not have active brain or spinal cord disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycles 1-8 and days 1 and 15 of subsequent cycles, and nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-8 and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 2 years.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Copanlisib Hydrochloride
• Nivolumab

Trial Overview The study tests the combination of Copanlisib Hydrochloride and Nivolumab in patients with recurrent or refractory diffuse large B-cell lymphoma. It aims to see if this combo can better inhibit tumor growth by blocking enzymes needed for cell growth and boosting the immune system's ability to fight cancer.

How Is the Trial Designed?

Group I: Treatment (copanlisib hydrochloride, nivolumab) Experimental Treatment 2 Interventions

Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8 and 15 of cycles 1-8 and days 1 and 15 of subsequent cycles. Patients also receive nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-8 and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12378973/

Results from the phase II multicentre FIL Copa‐BR trial from ... The 12‐m OS rate was 44.5%, with a median OS of 8.8 months. The efficacy of copa‐BR resulted in lower than expected and did not improve upon the results ...

2. 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 ... Giving copanlisib hydrochloride and nivolumab may work better in treating patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf

209936Orig1s000 - accessdata.fda.gov The efficacy of copanlisib was established in 104 patients with follicular lymphoma on the basis of an ORR of 58.7% with a median duration of ...

4. jmcp.org jmcp.org/doi/10.18553/jmcp.2019.18259

A Budget Impact Analysis of the Introduction of Copanlisib ... CONCLUSIONS: Over a 1-year period, the model found that the addition of copanlisib to a formulary resulted in a small increase in total budget ...

5. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/copanlisib

Copanlisib - an overview Copanlisib has been shown to inhibit cellular proliferation in various cancers including multiple myeloma, relapsed or refractory, indolent or aggressive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9813077/

Safety and antitumor activity of copanlisib in Japanese ... Overall, copanlisib 60 mg had an acceptable safety profile and showed promising antitumor activity in Japanese patients with relapsed/refractory indolent NHL.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03484819?term=AREA%5BConditionSearch%5D(%22Primary%20Mediastinal%20Large%20B-Cell%20Lymphoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22antineoplastic%20agents%22)&rank=10

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 ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S000649711862018X

626.Aggressive Lymphoma (Diffuse Large B-Cell and ... In a preclinical DLBCL mouse model, treatment with copanlisib resulted in effective down regulation of tumor‐infiltrating T-regulatory cells ( ...

9. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1034253/full

Efficacy and safety of copanlisib in relapsed/refractory B ... For all R/R B-NHL patients treated with copanlisib monotherapy, the common any grade toxicities were hyperglycemia (63.69%), hypertension (49.69%), diarrhea ( ...