Combination Immunotherapy + Chemotherapy for Pancreatic Cancer

Not currently recruiting at 3 trial locations

Overseen By Paula Bradshaw

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ImmunityBio, Inc.

Must be taking: Gemcitabine, Nab-paclitaxel

Must not be taking: Corticosteroids, CYP3A4 inhibitors

Disqualifiers: Autoimmune disease, Organ transplant, 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: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining immunotherapy, which uses the body's immune system, with chemotherapy for individuals with advanced pancreatic cancer. It compares standard chemotherapy to a combination of chemotherapy and new drugs such as aldoxorubicin HCl, N-803 (an IL-15 superagonist complex), and PD-L1 t-haNK (a type of immunotherapy). Participants are grouped based on their previous treatments and cancer progression. Individuals diagnosed with advanced pancreatic cancer who have undergone previous treatments without progression may be suitable for this study. As a Phase 2 trial, this research focuses on assessing 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 must stop taking your current medications. However, you cannot use certain medications like strong CYP3A4 or CYP2C8 inhibitors or inducers within 14 days before starting the study. 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 shows that the treatments in this trial, which include a mix of chemotherapy and immunotherapy, have shown promise in earlier studies. For example, the combination of N-803 and PD-L1 t-haNK, both part of the trial's investigational treatments, has been studied for its potential benefits. Reports suggest these treatments are generally well-tolerated when used together, with ongoing research supporting their combined use.

Aldoxorubicin, another component, has been used in cancer treatments before. It's a modified version of doxorubicin, a common chemotherapy drug, and it's designed to be less harmful than the original. Cyclophosphamide, gemcitabine, and nab-paclitaxel are also widely used in cancer therapy, with side effects that are usually manageable.

This trial is in phase 2, meaning the treatments have been tested in earlier stages for initial safety. However, side effects can still occur. Common side effects may include tiredness, low blood counts, and nausea, among others. Participants should discuss these potential risks with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they combine traditional chemotherapy with innovative immunotherapy strategies. Unlike standard treatments, which typically focus on chemotherapy alone, these investigational treatments incorporate agents like N-803 and PD-L1 t-haNK cells, which work to boost the body's immune response against cancer cells. This combination aims to enhance the effectiveness of chemotherapy by enabling the immune system to better recognize and attack the cancer, potentially leading to improved outcomes. Additionally, the use of aldoxorubicin, a novel form of doxorubicin, is designed to deliver the drug more effectively to cancer cells, reducing side effects and improving potency. These unique features offer hope for more effective and targeted treatment options for patients facing this challenging diagnosis.

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

Research shows that combining chemotherapy with immunotherapy may offer promise in treating pancreatic cancer. In this trial, participants will join different treatment arms. One arm includes a combination of precise radiation therapy, known as SBRT, with drugs such as cyclophosphamide, gemcitabine, nab-paclitaxel, aldoxorubicin, and N-803, which earlier studies have shown to be promising. This combination aims to attack cancer cells while strengthening the immune system, crucial for combating challenging cancers like pancreatic cancer. Another arm will add special immune cells called PD-L1 t-haNK cells, which early results suggest can improve survival rates by enhancing the body's natural defenses against cancer. Overall, these treatments offer hope by integrating traditional and new therapies to address this aggressive disease. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic pancreatic cancer who've had certain treatments and have specific responses can join. They must be able to follow the study plan, agree to use contraception, and not have other serious health issues or recent participation in other drug studies.

Inclusion Criteria

Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines

I have at least one tumor that can be measured or evaluated.

I can attend all required study visits and follow-ups.

Exclusion Criteria

My lab tests show my organs are not functioning well.

I have high blood pressure or heart problems that are not well-managed.

I have had an organ transplant and take medicine to prevent rejection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard-of-care chemotherapy with or without combination immunotherapy

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil
• Aldoxorubicin HCl
• Cyclophosphamide
• Gemcitabine
• Irinotecan liposome
• Leucovorin
• N-803
• Nab-paclitaxel
• PD-L1 t-haNK
• SBRT

Trial Overview The trial is testing if adding aldoxorubicin HCl, N-803, and PD-L1 t-haNK to standard chemotherapy works better for treating pancreatic cancer. It's an open-label phase 2 study with three separate groups based on previous treatment response.

How Is the Trial Designed?

Group I: Cohort C Experimental Treatment Arm Experimental Treatment 7 Interventions

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin + N-803 + PD-L1 t-haNK

Group II: Cohort B Experimental Treatment Arm Experimental Treatment 7 Interventions

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK

Group III: Cohort A Experimental Treatment Arm 2 Experimental Treatment 7 Interventions

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel+ aldoxorubicin HCl + N-803 + PD-L1 t-haNK

Group IV: Cohort A Experimental Treatment Arm 1 Experimental Treatment 6 Interventions

SBRT + cyclophosphamide + gemcitabine + nab-paclitaxel + aldoxorubicin HCl + N-803

Group V: Cohort A Control Treatment Arm Active Control 3 Interventions

SBRT + gemcitabine + nab-paclitaxel

Group VI: Cohort B Control Treatment Arm Active Control 3 Interventions

Irinotecan liposome + 5-FU/leucovorin

5-Fluorouracil is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Ovarian cancer

Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer

Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

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

In a real-world study of 86 patients with metastatic pancreatic adenocarcinoma who received nal-IRI plus 5-FU/LV after gemcitabine therapy, the median overall survival was 9.4 months, indicating that this treatment is effective in this patient population.

The treatment was generally well-tolerated, with the most common severe side effects being neutropenia (37.2%) and nausea (10.5%), suggesting a manageable safety profile similar to findings from the NAPOLI-1 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group. Yoo, C., Im, HS., Kim, KP., et al.[2022]

The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy significantly improved treatment outcomes for metastatic pancreatic cancer, with response rates increasing from 7.8% to 28.4% after these therapies were introduced.

Patients treated with the newer therapies experienced longer median progression-free survival (3.1 months to 5.4 months) and median overall survival (6.7 months to 10.2 months), indicating a substantial benefit in daily clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. Sasaki, T., Kanata, R., Yamada, I., et al.[2022]

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

Neoadjuvant FOLFIRINOX therapy for borderline resectable pancreatic cancer was found to be safe, with no in-hospital or 30-day mortalities, and it resulted in a high resection rate of 67% among treated patients.

The study showed that 58.3% of patients who completed the therapy are alive, with 5 having no evidence of disease, indicating promising efficacy in improving survival outcomes compared to previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Christians, KK., Tsai, S., Mahmoud, A., et al.[2022]

In a study of 1102 patients with metastatic pancreatic cancer, FOLFIRINOX treatment resulted in a median overall survival of 9.27 months, significantly longer than the 6.87 months observed with gemcitabine plus nab-paclitaxel (P < 0.001).

Patients receiving FOLFIRINOX also experienced 17.3% fewer posttreatment hospitalizations and 20% lower posttreatment costs compared to those treated with gemcitabine plus nab-paclitaxel, indicating better safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. Klein-Brill, A., Amar-Farkash, S., Lawrence, G., et al.[2023]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

The sequential treatment of nab-paclitaxel/gemcitabine followed by FOLFIRINOX in metastatic pancreatic cancer showed a high objective response rate of 64.9% and acceptable toxicity, with no deaths reported during the study.

Patients experienced manageable side effects, primarily neutropenia and venous thromboembolism, while achieving a median progression-free survival of 10.5 months and overall survival of 15.1 months, indicating the treatment's potential effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential first-line treatment with nab-paclitaxel/gemcitabine and FOLFIRINOX in metastatic pancreatic adenocarcinoma: GABRINOX phase Ib-II controlled clinical trial. Assenat, E., de la Fouchardière, C., Portales, F., et al.[2022]

In a study of 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., et al.[2022]

In a phase II trial involving 21 patients with untreated advanced pancreatic cancer, the combination treatment of trimetrexate, leucovorin, and 5-fluorouracil (NFL) was found to be well-tolerated, with serious toxicities occurring in a minority of patients (23.8% experienced Grade 3 diarrhea).

The treatment resulted in a median survival of 6.8 months and a 1-year survival rate of 19%, which is comparable to other available treatment options for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer. Garcia, AA., Leichman, L., Baranda, J., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04390399

Study Details | NCT04390399 | Combination ... This is a phase 2, three-cohort (2 randomized and 1 single-arm), open-label study to evaluate the comparative efficacy and overall safety of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25171298/

Stereotactic Body Radiation Therapy (SBRT) Combined ... SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible, and generally well tolerated. Outcomes of SBRT combined with ...

3. researchgate.net researchgate.net/publication/388896126_Case_report_PD-L1-targeted_high-affinity_natural_killer_cells_and_IL-15_superagonist_N-803-based_therapy_extend_overall_survival_of_advanced_metastatic_pancreatic_cancer_patients

Case report: PD-L1-targeted high-affinity natural killer cells ... ... stereotactic body radiation therapy (SBRT ... This study investigates outcomes of treatment with erlotinib plus gemcitabine for unresectable pancreatic cancer.

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1472714/full

Case report: PD-L1-targeted high-affinity natural killer cells ... The findings here support the ongoing clinical investigations of N-803 and PD-L1 t-haNK cells in combination therapy.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8827285/

Combination therapy for pancreatic cancer: anti-PD-(L)1 ... Mortality associated with pancreatic cancer is among the highest of all malignancies, with a 5-year overall survival of 5–10%.

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/98/NCT03387098/Prot_SAP_000.pdf

NANT PANCREATIC CANCER VACCINE The treatment regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, cyclophosphamide,. Ad5-based vaccine (ETBX-011), 5-FU/leucovorin, yeast-based ...

7. targetedonc.com targetedonc.com/view/novel-cancer-vaccine-yields-promising-survival-rates-in-pancreatic-cancer

Novel Cancer Vaccine Yields Promising Survival Rates in ... A doubling of survival in third-line patients with metastatic pancreatic cancer when treated with the novel combination immunotherapy protocol.