Copanlisib + Venetoclax for Lymphoma

Not currently recruiting at 3 trial locations

Overseen By Jennifer Crombie, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A inhibitors, Herbal medications

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of two drugs, copanlisib and venetoclax, to determine their effectiveness in treating diffuse large B-cell lymphoma (DLBCL) that has returned or is unresponsive to other treatments. The trial will explore different doses to identify the optimal level for effectiveness and safety. Suitable candidates for this trial include those with DLBCL who have previously undergone treatments like stem cell transplantation or CAR T-cell therapy but require additional options. 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 must stop taking your current medications, but it does exclude certain medications. You cannot take strong inhibitors or inducers of CYP3A, certain anticoagulants like warfarin, or herbal medications within 7 days of starting the study treatment. It's best to discuss your current medications with the study team.

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

Research has shown that using copanlisib and venetoclax together is generally safe for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Studies have found that adding venetoclax does not significantly increase serious blood-related side effects. No reports of severe anemia (a condition with too few red blood cells) or thrombocytopenia (a condition with too few platelets, which help blood clot) have emerged.

Additionally, other studies have found that this drug combination is safe and manageable, as no serious side effects were observed that would prevent increasing the dose. Patients can handle the treatment well, even at higher doses. Another study noted that copanlisib alone was well-tolerated, with no significant weight loss or negative effects reported.

Overall, these findings suggest that the combination therapy is promising in terms of safety and is being carefully studied to ensure it is well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for lymphoma involve chemotherapy, immunotherapy, or radiation, targeting cancer cells broadly. However, copanlisib and venetoclax offer a unique approach. Copanlisib works by inhibiting the PI3K pathway, a critical pathway for cancer cell growth and survival, while venetoclax targets and inhibits BCL-2, a protein that helps cancer cells evade death. This combination specifically hones in on these pathways, potentially offering a more targeted attack on lymphoma cells. Researchers are excited because this dual-targeting strategy could lead to more effective treatments with possibly fewer side effects compared to traditional therapies.

What evidence suggests that this combination treatment could be effective for lymphoma?

Research has shown that using copanlisib and venetoclax together may help treat certain types of lymphoma, such as diffuse large B-cell lymphoma (DLBCL). This trial will explore the combination of copanlisib and venetoclax in two different treatment arms. One arm will focus on dose escalation to determine the optimal dosing strategy, while the other will administer the combination at the recommended phase II dose (RP2D). Some studies have tested this drug combination in patients with mantle cell lymphoma, another type of blood cancer, and the results were promising. Lab tests suggest that venetoclax works well with copanlisib to fight B-cell lymphomas, including DLBCL. However, early trials in DLBCL patients showed only a modest response. This indicates potential, but more research is needed to understand the treatment's effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Jennifer Crombie, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults (≥18 years) with relapsed/refractory diffuse large B-cell lymphoma who have failed or are ineligible for stem cell transplant or CAR T-cell therapy. Participants must have adequate organ function, no severe autoimmune diseases, no recent major surgeries, and not be pregnant. They should agree to use effective contraception.

Inclusion Criteria

Total bilirubin ≤ 1.5 x ULN (< 3 x ULN for patients with Gilbert's syndrome, patients with cholestasis due to compressive adenopathies of the hepatic hilum or documented liver involvement or with biliary obstruction due to lymphoma)

My condition worsened after stem cell transplant or CAR T-cell therapy, or I can't have these treatments.

My platelet count is above 75,000 or above 50,000 if cancer has spread to my bone marrow.

Exclusion Criteria

I take medication for seizures.

I finished IV antibiotics for an infection less than a week ago or have an ongoing infection.

I am on preventive antibiotics with no active infection and my medication is not prohibited.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation of copanlisib and venetoclax to determine the maximum tolerated dose

28 days up to 1 year

Copanlisib IV on days 1, 8, and 15; Venetoclax orally daily

Phase II Treatment

Treatment with copanlisib and venetoclax at the recommended phase II dose

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months up to 1 year

Long-term Follow-up

Monitoring overall survival and progression-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Copanlisib
• Venetoclax

Trial Overview The trial is testing a combination of two drugs, copanlisib and venetoclax, as potential treatments for those with difficult-to-treat B-cell lymphoma that has returned after treatment or hasn't responded to previous therapies.

How Is the Trial Designed?

Group I: Recommended phase II dose (RP2D) Copanlisib + Venetoclax Experimental Treatment 2 Interventions

Patients will be treated with copanlisib in combination with venetoclax, administered at the Recommended phase II dose (RP2D).

Group II: Dose Escalation Copanlisib + Venetoclax Experimental Treatment 2 Interventions

Phase 1 * Dose escalation will occur using a 3+3 design * Copanlisib will be administered IV on days 1, 8 and 15 in 28 day cycle * Venetoclax will be administered orally daily for each 28-day cycle. During cycle 1, a venetoclax dose ramp-up is performed in the outpatient setting

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

The combination of venetoclax and obinutuzumab was found to be safe and well-tolerated in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia, with no dose-limiting toxicities observed during the study.

The treatment resulted in a high overall response rate of 95% in relapsed/refractory patients and 100% in previously untreated patients, with significant rates of undetectable minimal residual disease, indicating effective disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Flinn, IW., Gribben, JG., Dyer, MJS., et al.[2021]

In a study involving 272 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), higher concentrations of venetoclax led to a quicker reduction in lymphocyte counts and tumor size, resulting in a high objective response rate (ORR) of 84.8% at a daily dose of 400 mg.

Importantly, increasing the dose of venetoclax did not correlate with a higher risk of serious adverse events like neutropenia or infections, suggesting that the 400 mg daily regimen is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. Freise, KJ., Jones, AK., Eckert, D., et al.[2018]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04939272

Study Details | NCT04939272 | Copanlisib and Venetoclax ... This phase I/II trial studies the side effects, best dose, and effectiveness of copanlisib and venetoclax in treating patients with mantle cell lymphoma ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04572763

NCT04572763 | Copanlisib Plus Venetoclax in R/R DLBCL This research study is evaluating the combination of two drugs, copanlisib and venetoclax, as a possible treatment for trelapsed/refractory diffuse large ...

3. researchgate.net researchgate.net/publication/397132296_Copanlisib_in_combination_with_venetoclax_in_patients_with_relapsedrefractory_mantle_cell_lymphoma?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJqb3VybmFsIiwicHJldmlvdXNQYWdlIjpudWxsLCJzdWJQYWdlIjoib3ZlcnZpZXcifX0

Copanlisib in combination with venetoclax in patients ... Ibrutinib plus venetoclax, given with an ibrutinib lead-in, has shown encouraging clinical activity in early phase studies in mantle cell lymphoma (MCL). The ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7065481/

and T-cell lymphoma models - PMC - PubMed Central A combination cell-viability screen for copanlisib partners identified venetoclax as the strongest one in BCLs. These data support the rationale for the ...

5. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper181067.html

A Phase I Study of Copanlisib and Venetoclax in Patients ... The overall response rate (ORR) and complete metabolic response (CMR) rate was 8% (90% CI: 0 - 34%), as 1 pt in DL +1, who had received >5 lines ...

6. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2025.2566316?src=

Copanlisib in combination with venetoclax in patients ... The addition of venetoclax did not appear to significantly worsen the hematologic toxicity profile, since no grade ≥3 anemia or thrombocytopenia ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1735/501493/A-Phase-I-Study-of-Copanlisib-and-Venetoclax-in

A Phase I Study of Copanlisib and Venetoclax in Patients with ... Conclusions: Copanlisib plus venetoclax is feasible and safe in pts with R/R DLBCL, with no DLTs observed. While it is possible that copanlisib ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123083386

A Phase I Study of Copanlisib and Venetoclax in Patients ... Conclusions: Copanlisib plus venetoclax is feasible and safe in pts with R/R DLBCL, with no DLTs observed. While it is possible that copanlisib ...