PI3Kinase Inhibition + Anti-PD-1 Antibody for Colorectal Cancer

Overseen By Joann Santmyer, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunotherapy, PI3K inhibitors, CYP3A4

Disqualifiers: CNS metastases, Active infection, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for colorectal cancer that has returned or isn't responding to other treatments. Researchers are testing two drugs: copanlisib, which targets cancer cell growth, and nivolumab, an anti-PD-1 antibody that helps the immune system fight cancer. Different groups in the trial assess how these drugs work together for various genetic profiles of the cancer. This trial may suit individuals with colorectal cancer who have tried several treatments without success and have a form of the disease that can be measured and biopsied. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop using CYP3A4 inhibitors and inducers (types of drugs that affect how your body processes other medications) within 2 weeks of starting the study drug and throughout the treatment. If you are on these medications, you will need to stop them before joining the trial.

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

Research has shown that using copanlisib and nivolumab together is generally safe for patients. In earlier studies, individuals with advanced solid tumors tolerated this treatment well, experiencing no unexpected or severe side effects beyond those typically associated with these drugs.

Another study found that the side effects of copanlisib and nivolumab were manageable, indicating they were neither too severe nor surprising.

This treatment has shown promise in treating certain types of cancer, such as colorectal cancer. However, safety can vary from person to person, so discussing any concerns with a healthcare provider is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Copanlisib and Nivolumab for colorectal cancer because they target the disease in new ways. Unlike standard chemotherapy, which attacks rapidly dividing cells, Copanlisib inhibits PI3Kinase, a protein that helps cancer cells grow, while Nivolumab harnesses the immune system by blocking PD-1, a protein that prevents immune cells from attacking cancer. This dual approach could lead to more effective and personalized treatments, especially for patients with specific genetic profiles. By combining these targeted therapies, there's potential for improved outcomes with fewer side effects compared to traditional treatments.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that using copanlisib and nivolumab together may help treat certain cancers, such as colorectal cancer. In this trial, participants will receive this combination. One study found that it provided long-lasting benefits for patients with a type of colorectal cancer that is usually hard to treat. Specifically, the treatment shrank or halted tumor growth in patients with advanced cancer. It was generally well tolerated, meaning it did not cause severe side effects. These findings suggest that this combination could be a promising option for people with specific types of colorectal cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Nilofer Azad, MD

Principal Investigator

Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors, including colorectal cancer that's still growing despite treatment. They must have tried at least two other treatments and be in good physical shape (able to perform daily activities). Participants need functioning organs, measurable disease for tracking progress, and the ability to provide consent. Pregnant or breastfeeding women can't join, nor can those with recent serious health issues like heart attacks or infections.

Inclusion Criteria

I am fully active or can carry out light work.

I've completed all treatments meant to cure me and have had at least 2 types of systemic therapy.

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

Cytomegalovirus polymerase chain reaction (CMV PCR) positive

I have been treated with a PI3K inhibitor before.

I am on medication for seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Copanlisib and Nivolumab for relapsed/refractory solid tumors

6 months

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Extension

Participants may continue to be monitored for long-term outcomes such as overall survival

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Copanlisib
• Nivolumab

Trial Overview The trial is testing Copanlisib, a PI3Kinase inhibitor, alongside Nivolumab, an anti-PD-1 antibody. It aims to see how well they work together in patients whose colorectal cancer hasn't responded to standard treatments. The study will monitor safety and effectiveness of this combination therapy.

How Is the Trial Designed?

Group I: Phase II/Arm B -P13K wild type /Copanlisib and Nivolumab Experimental Treatment 2 Interventions

Group II: Phase II /Arm A-P13K mutation/Copanlisib and Nivolumab Experimental Treatment 2 Interventions

Group III: Phase I - Copanlisib and Nivolumab (De-Escalation) Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

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

The PI3Kα inhibitor alpelisib demonstrated a 58.2% disease control rate in patients with solid tumors that have PIK3CA alterations, indicating its potential efficacy in this specific cancer population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PI3Kα Inhibitor Alpelisib Has Activity in PIK3CA-altered Tumors. [2019]

PD-1/PD-L1 inhibitors used in treating non-small cell lung cancer (NSCLC) are associated with a significantly higher risk of immune-related colitis, with an overall incidence of 1.40% for all grades and 0.89% for severe cases, compared to chemotherapy.

While PD-1 inhibitors specifically increase the risk of colitis, they may also reduce the risk of all-grade diarrhea, indicating a complex safety profile that clinicians need to consider when prescribing these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The incidence and relative risk of PD-1/PD-L1 inhibitors-related colitis in non-small cell lung cancer: A meta-analysis of randomized controlled trials. Lin, LL., Lin, GF., Luo, Q., et al.[2020]

In a phase II trial involving 48 patients with microsatellite stable colorectal cancer, the combination of regorafenib and avelumab showed a best response of stable disease in 53.5% of patients, with a median progression-free survival of 3.6 months and overall survival of 10.8 months.

The study found that higher infiltration of CD8+ T cells in tumors was linked to better outcomes, suggesting that assessing immune cell presence could help identify patients who might benefit more from this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib-Avelumab Combination in Patients with Microsatellite Stable Colorectal Cancer (REGOMUNE): A Single-arm, Open-label, Phase II Trial. Cousin, S., Cantarel, C., Guegan, JP., et al.[2022]

In a meta-analysis of clinical trials, PD-1 inhibitors (like nivolumab and pembrolizumab) were found to have a higher incidence of colitis compared to PD-L1 inhibitors (like atezolizumab and durvalumab), with rates of 1.49% for all grade colitis and 0.85% for grade 3-4 colitis.

The analysis indicated that the relative risk of developing colitis with PD-1 inhibitors was significantly higher (1.80 for all grade colitis and 2.52 for grade 3-4 colitis), suggesting that patients receiving PD-1 inhibitors may need closer monitoring for this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Risk of Colitis With Programmed Death 1 Versus Programmed Death Ligand 1 Inhibitors for the Treatment of Cancer. Miyashita, H., Mikami, T., Satoi, S., et al.[2021]

Programmed cell death 1 (PD-1) and its ligand (PD-L1) are promising targets for treating gastrointestinal cancers, which are a leading cause of cancer-related deaths, highlighting the need for new biomarkers and therapies.

Several PD-1/PD-L1 inhibitors, including pembrolizumab, have been developed and approved for use in other cancers, showing potential for improving treatment efficacy in gastrointestinal cancers, although resistance mechanisms to these therapies are still being studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed cell death 1 as prognostic marker and therapeutic target in upper gastrointestinal cancers. Khoshghamat, N., Jafari, N., Moetamani-Ahmadi, M., et al.[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]

Citations

1. onclive.com onclive.com/view/dr-christenson-on-the-safety-of-copanlisib-plus-nivolumab-in-pretreated-mss-mcrc

Dr Christenson on the Safety of Copanlisib Plus ... - OncLive Efficacy data presented at the 2024 AACR Annual Meeting showed copanlisib in combination with nivolumab exhibited durable responses in patients ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03711058

NCT03711058 | Study of PI3Kinase Inhibition (Copanlisib) ... A phase I/II study of PI3Kinase inhibition (copanlisib) and anti-PD-1 antibody nivolumab in relapsed/refractory solid tumors with expansions in mismatch-repair ...

3. aacrjournals.org aacrjournals.org/cancerrescommun/article-pdf/5/3/444/3557433/crc-24-0407.pdf

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

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7886024/

Immunotherapy efficacy on mismatch repair-deficient ... This clinical trial recently reported a remarkable improvement in median PFS of 16.5 months versus 8.2 months, and objective response rate (ORR) of 43.8% versus ...

5. withpower.com withpower.com/trial/phase-2-colonic-neoplasms-2019-af723

PI3Kinase Inhibition + Anti-PD-1 Antibody for Colorectal ... A case report showed that a PD-1 inhibitor, similar to Nivolumab and Opdivo, combined with another drug, demonstrated good effectiveness in a specific type of ...

6. 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.

7. onclive.com onclive.com/view/copanlisib-plus-nivolumab-demonstrates-activity-in-microsatellite-stable-colorectal-cancer

Copanlisib Plus Nivolumab Demonstrates Activity in ... Copanlisib (Aliqopa) in combination with nivolumab (Opdivo) led to durable responses in patients with microsatellite stable (MSS) colorectal cancer (CRC).

8. 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.