Combination Immunotherapy for Cancer

Not currently recruiting at 35 trial locations

Overseen By Joseph Ward

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ImmunityBio, Inc.

Must be taking: Anti-PD-1, Anti-PD-L1

Must not be taking: Immunosuppressants, Systemic steroids

Disqualifiers: Autoimmune disease, Organ transplant, Hepatitis, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of immunotherapy treatments for individuals with advanced solid tumors. It targets those who have previously tried PD-1/PD-L1 checkpoint inhibitors without lasting results. The trial aims to assess the safety and effectiveness of these new combinations in combating cancer and enhancing the body's immune response. Suitable candidates have advanced cancers, such as lung cancer or melanoma, and have already received treatments like pembrolizumab (KEYTRUDA) or nivolumab (Opdivo), but their cancer has progressed. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroids or immunosuppressive medications, you must stop them at least 3 days before starting the study, unless they are used for daily steroid replacement or managing side effects.

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

In a previous study, researchers administered avelumab to 1,300 patients with advanced cancer. Most handled the treatment well, but some stopped due to side effects, with 11.9% discontinuing because of issues during treatment. Common side effects included fatigue, nausea, and infusion-related reactions.

Research has shown that durvalumab is safe for many types of solid cancers. When combined with other drugs, it was generally manageable, and serious side effects were rare. The most common issues were fatigue and loss of appetite.

N-803, now approved by the FDA for bladder cancer, was tested with 160 patients. It had a low chance of causing severe reactions, indicating general safety. Most side effects were mild, such as flu-like symptoms.

Nivolumab, tested for melanoma and bladder cancer, demonstrated a good safety record. A small number of patients experienced serious reactions like heart and lung issues, but these were rare. More common side effects included fatigue and muscle pain.

Studies have shown that pembrolizumab maintains a consistent safety record. Across many trials, it was mostly safe, with common side effects being fatigue, itchy skin, and diarrhea. Serious issues were less common but included liver and lung problems.

Overall, these treatments have demonstrated a reasonable safety record in previous studies, with most side effects being mild and manageable. However, as with any treatment, there is always a risk of more severe reactions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these combination immunotherapies for cancer because they introduce a novel approach by using multiple checkpoint inhibitors together. Unlike standard treatments, which typically involve single-agent checkpoint inhibitors like pembrolizumab or nivolumab, this combination therapy aims to overcome resistance developed after initial treatment responses. Avelumab, Durvalumab, N-803, Nivolumab, and Pembrolizumab are used in various combinations to target different pathways in the immune system, potentially enhancing the anti-cancer response. This multi-pronged attack could provide new hope for patients who have progressed after standard immunotherapy options, offering the possibility of a more robust and sustained treatment effect.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

This trial will explore the effectiveness of various immunotherapy drugs, including avelumab, durvalumab, N-803, nivolumab, and pembrolizumab, in treating different cancers. Research has shown that avelumab helps patients with bladder cancer live longer when used as a follow-up treatment. Specifically, durvalumab demonstrated that 66.3% of patients with non-small cell lung cancer (NSCLC) were still alive after 24 months. N-803, used for bladder cancer, has resulted in a high survival rate, with some patients becoming completely cancer-free. Nivolumab has proven effective for NSCLC, with many patients experiencing long-lasting benefits. Pembrolizumab has increased survival rates in advanced melanoma. These treatments, studied in separate cohorts of this trial, have shown effectiveness in certain cancers, offering hope for patients who have tried other therapies. ^{4 6 7 8 9}

Who Is on the Research Team?

Chad Garner, PhD

Principal Investigator

ImmunityBio, Inc.

Are You a Good Fit for This Trial?

This trial is for adults (18+) who've had prior treatment with PD-1/PD-L1 checkpoint inhibitors for various cancers, including lung, colorectal, and melanoma. They should have an ECOG performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must not be pregnant or nursing and agree to use effective contraception.

Inclusion Criteria

Voluntary written informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations

I am a woman who can have children and have tested negative for pregnancy.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You have hepatitis B infection or have tested positive for hepatitis C.

I have not had heart failure, chest pain, or a heart attack in the last 6 months.

No other illness that in the opinion of the investigator would exclude the subject from participating in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination immunotherapy with N-803 and a PD-1/PD-L1 checkpoint inhibitor, with additional treatments in specific cohorts

Up to 24 months

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Durvalumab
• N-803
• Nivolumab
• PD-L1 t-haNK
• Pembrolizumab

Trial Overview The study tests combinations of immunotherapies: N-803 with different checkpoint inhibitors like Nivolumab and Avelumab, plus a cellular therapy called PD-L1 t-haNK for some patients. It's an open-label Phase IIb trial where treatments last up to two years with cycles every six weeks.

How Is the Trial Designed?

Group I: Cohort 6 Experimental Treatment 2 Interventions

Patients who have progressed after an initial response (CR or PR) to a PD-1/PD-L1 checkpoint inhibitor but now exhibit acquired resistance. They have received exactly one line of anti-PD-1 or anti-PD-L1 therapy (either pembrolizumab or nivolumab) for advanced NSCLC (Stage IV or recurrent).

Group II: Cohort 5 Experimental Treatment 5 Interventions

Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.

Group III: Cohort 4 Experimental Treatment 5 Interventions

Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.

Group IV: Cohort 3 Experimental Treatment 2 Interventions

Patients with NSCLC who had an initial CR or PR but subsequently relapsed on maintenance PD-1 checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy in combination with chemotherapy as first-line treatment.

Group V: Cohort 2 Experimental Treatment 2 Interventions

Patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%) and who relapsed on a PD-1 checkpoint inhibitor after experiencing an initial CR or PR when they received checkpoint inhibitor as a single-agent for first-line treatment.

Group VI: Cohort 1 Experimental Treatment 5 Interventions

Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor. 1a - Non-small cell lung cancer 1b - Small cell lung cancer 1c - Urothelial carcinoma 1d - Head and neck squamous cell carcinoma 1e - Merkel cell carcinoma 1f - Melanoma 1g - Renal cell carcinoma 1h - Gastric cancer 1i - Cervical cancer 1j - Hepatocellular carcinoma 1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer

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

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

ImmunityBio, Inc.

Lead Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., et al.[2022]

A phase I study found that the combination of utomilumab, an investigational antibody targeting CD137, and pembrolizumab is safe and well tolerated in patients with various solid cancers.

This combination therapy resulted in sustained responses, suggesting potential efficacy in treating these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing PD-1 Blockade in Solid Tumors. [2021]

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]

In a meta-analysis of 15 studies involving cancer patients treated with either nivolumab or pembrolizumab, nivolumab was associated with a higher overall incidence of cardiotoxicity (55.7%) compared to pembrolizumab (27.31%), although this difference was not statistically significant.

However, when looking specifically at myocarditis, pembrolizumab showed a significant increase in cardiotoxicity risk, suggesting that while nivolumab may be more commonly reported for general cardiotoxicity, pembrolizumab poses a greater risk for this specific heart condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. Ndjana Lessomo, FY., Wang, Z., Mukuka, C.[2023]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

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Locally Advanced or Metastatic UC Learn about BAVENCIO® (avelumab) as the first and only immunotherapy approved for the first-line maintenance treatment of metastatic urothelial carcinoma.