Combination Immunotherapy + Chemotherapy for Pancreatic Cancer

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

328 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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 standard-of-care chemotherapy versus standard-of-care chemotherapy in combination with aldoxorubicin HCl, N-803, and PD-L1 t-haNK in subjects with locally advanced or metastatic pancreatic cancer. Each treatment setting (ie, first line maintenance, second line, or third line or greater) will be evaluated independently as a separate cohort.

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.

What safety data exists for combination immunotherapy and chemotherapy in pancreatic cancer?

The combination of 5-fluorouracil, nab-paclitaxel, leucovorin, and oxaliplatin (FABLOx) was found to be feasible and tolerable in patients with metastatic pancreatic cancer, though some patients experienced severe side effects like anemia and mucositis (painful inflammation of the mouth). Another study showed that liposomal irinotecan with 5-fluorouracil and leucovorin was well-tolerated in patients whose cancer progressed on other treatments. ^{1 2 3 4 5}

How is the combination immunotherapy and chemotherapy treatment for pancreatic cancer different from other treatments?

This treatment combines multiple drugs, including 5-fluorouracil, gemcitabine, and nab-paclitaxel, which have shown improved survival rates in pancreatic cancer compared to single-agent therapies. It uniquely integrates both chemotherapy and immunotherapy, potentially offering a more comprehensive approach to targeting cancer cells. ^{6 7 8 9 10}

What data supports the effectiveness of the drug combination used in the clinical trial for pancreatic cancer?

Research shows that combinations like FOLFIRINOX (which includes 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel improve survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. ^{1 6 7 11 12}

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

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]

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]

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]

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 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]

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]

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 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. United States 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. [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. [2022]

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

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

5. England 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. [2022]

6. England 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. [2022]

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

A randomised phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel for locally advanced pancreatic cancer (JCOG1407). [2023]

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

A Phase I/II Open-Label Multicenter Single-Arm Study of FABLOx (Metronomic 5-Fluorouracil Plus nab-Paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin) in Patients with Metastatic Pancreatic Cancer. [2023]

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

Comparison of FOLFIRINOX vs Gemcitabine Plus Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Systemic therapy for advanced pancreatic cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? [2022]

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

Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer. [2018]