Copanlisib + Durvalumab for Lung Cancer

(LCD Trial)

Overseen By Yvonne Taul, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Zhonglin Hao

Must be taking: Durvalumab

Must not be taking: Immunosuppressants, Steroids, Investigational agents

Disqualifiers: Autoimmune disease, Transplant, Lung disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

11 Participants Needed

Trial Summary

What is the purpose of this trial?

The current study focuses on unresectable stage III non-small cell lung cancer (NSCLC) patients who are starting Durvalumab consolidation after concurrent chemoradiation with a goal of cure. The overall hypothesis of this study is that the addition of Copanlisib to Durvalumab will be well-tolerated at a biweekly schedule. It will test whether the addition of Copanlisib to Durvalumab can overcome resistance to Durvalumab.

Will I have to stop taking my current medications?

The trial information does not clearly state if you must stop taking your current medications. However, it mentions that you cannot be on other investigational agents or certain medications prohibited by the study. It's best to discuss your current medications with the trial team to see if they are allowed.

What safety information is available for Copanlisib and Durvalumab in humans?

Durvalumab, also known as Imfinzi or MEDI4736, has been associated with an increased risk of immune-related side effects, particularly pneumonitis (inflammation of the lungs), which can be serious and potentially life-threatening. This safety information is based on its use in treating various cancers, including lung cancer. ^{1 2 3 4 5}

What makes the drug combination of Copanlisib and Durvalumab unique for lung cancer treatment?

The combination of Copanlisib and Durvalumab for lung cancer is unique because it pairs a PI3K inhibitor (Copanlisib) with an immune checkpoint inhibitor (Durvalumab), potentially offering a novel approach by targeting both cancer cell growth and the immune system's ability to fight cancer. ^{6 7 8 9 10}

Research Team

Zhonglin Hao

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for adults with stage III non-small cell lung cancer (NSCLC) that can't be removed by surgery. They should have received chemoradiation and are about to start Durvalumab therapy. Participants need at least one measurable lesion, good performance status, proper organ function, and must understand and sign consent forms. People with certain heart conditions, mixed lung cancers, specific gene mutations, or on prohibited medications cannot join.

Inclusion Criteria

My lung cancer is confirmed and cannot be removed by surgery, but I have had chemoradiation.

I will start Durvalumab as a follow-up treatment.

You have at least one spot that can be measured to see if the treatment is working.

Exclusion Criteria

I have not had any major surgeries in the last 28 days.

I have not had serious bleeding issues in the last month.

I have received chemotherapy and radiation therapy one after the other.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-finding

Participants receive Copanlisib and Durvalumab to determine the appropriate dose

28 days

2 visits (in-person)

Dose-expansion

Participants are treated at the recommended dose to confirm safety and initial efficacy

10 years

Biweekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Treatment Details

Interventions

• Copanlisib
• Durvalumab

Trial Overview The study tests if adding Copanlisib to Durvalumab after chemoradiation improves outcomes in NSCLC patients aiming for a cure. It examines the safety of combining these drugs biweekly and whether this combination can help overcome resistance to Durvalumab alone.

Participant Groups

Group I: Copanlisib (30-60mg iv) Experimental Treatment 2 Interventions

Patients in the group will receive Durvalumab at 10mg/kg (IV infusion on days 1 and 15, q28 days or 1500mg day 1 q28d). They will also receive Copanlisib ranging from 30mg to 60mg (IV infusion on days 1 and 15, q 28 days).

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Zhonglin Hao

Lead Sponsor

Trials

4

Recruited

50+

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

Findings from Research

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

A review of 2217 adverse drug reaction reports related to immune checkpoint inhibitors (ICIs) from 2011 to 2018 revealed that these drugs, particularly nivolumab, are associated with a higher frequency of serious immune-related adverse events, including gastrointestinal and respiratory disorders.

Emerging safety signals, such as ischaemic heart disease and cardiac failure, were identified, indicating the need for further investigation into the long-term safety profile of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. Cutroneo, PM., Isgrò, V., Ientile, V., et al.[2021]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

Methotrexate (MTX) is the most commonly used drug in combination therapies for rheumatoid arthritis, showing the best results when paired with leflunomide, cyclosporine, or in a triple combination with sulphasalazine and hydroxychloroquine.

Combining MTX with biologics, especially TNF inhibitors, abatacept, rituximab, or tocilizumab, enhances treatment efficacy and helps prevent disease progression, with safety profiles similar to individual medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination therapy using methotrexate with DMARDs or biologics--current status]. Krüger, K.[2021]

In a study of 3162 adults with rheumatoid arthritis, rituximab and tocilizumab showed significantly longer durations of survival without treatment failure compared to abatacept, with average durations of 19.8 months and 19.1 months respectively, versus 15.6 months for abatacept.

No significant differences were found in safety outcomes, such as serious infections or cardiovascular events, indicating that while rituximab and tocilizumab may be more effective, they do not pose additional safety risks compared to abatacept.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. Gottenberg, JE., Morel, J., Perrodeau, E., et al.[2020]

In a study of 8,394 patients, subcutaneous (SC) methotrexate (MTX) showed higher continuation rates compared to oral MTX, with a rate ratio of 1.54, indicating better tolerance and adherence to treatment.

SC MTX was associated with significantly fewer adverse events compared to biologic and combination therapies, suggesting it is a safer option in routine clinical practice, despite being administered at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Subcutaneous Methotrexate in Routine Clinical Practice. Li, CKH., Baker, K., Jones, T., et al.[2022]

Certolizumab pegol (CZP) combined with methotrexate (MTX) significantly improved the ACR20 response rate in patients with active rheumatoid arthritis compared to placebo + MTX, with higher efficacy observed at the 400 mg dosage.

The safety profile of CZP + MTX was comparable to that of MTX alone, as there were no significant differences in the number of adverse event-related withdrawals among the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of methotrexate plus certolizumab pegol or placebo in active rheumatoid arthritis : Meta-analysis of randomized controlled trials. Lee, YH., Bae, SC.[2019]

In a long-term study of 1681 rheumatoid arthritis patients over 4 years, methotrexate (MTX) was found to be the most effective treatment, with 39.6% of patients continuing its use, compared to lower retention rates for other medications like azathioprine (28.3%) and chloroquine (6.6%).

The study also revealed that the majority of patients who discontinued treatment did so within the first year due to side effects, with methotrexate, azathioprine, and sulfasalazine having drop-out rates due to toxicity around 15-17%, while chloroquine had a higher drop-out rate of 34.8%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term application of disease modifying antirheumatic drugs (DMARD). A single-center, observational study of 1681 patients with rheumatoid arthritis (RA). Keysser, M., Keysser, G., Keysser, C.[2019]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

[Combination therapy using methotrexate with DMARDs or biologics--current status]. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Subcutaneous Methotrexate in Routine Clinical Practice. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of methotrexate plus certolizumab pegol or placebo in active rheumatoid arthritis : Meta-analysis of randomized controlled trials. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Long-term application of disease modifying antirheumatic drugs (DMARD). A single-center, observational study of 1681 patients with rheumatoid arthritis (RA). [2019]