Combination Therapy for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gulam Manji

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: Autoimmune disease, CNS metastases, 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: 16 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of standard chemotherapy, an immune-boosting drug, and a new drug to treat aggressive pancreatic cancer. The goal is to see if this mix can shrink tumors and help patients live longer. The treatment aims to kill cancer cells directly and enhance the body's immune response against the cancer. Gemcitabine is currently the standard treatment for advanced pancreatic cancer.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or certain immunosuppressive medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination therapy for pancreatic cancer?

Research shows that combining nab-paclitaxel (Abraxane) with gemcitabine improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This combination has demonstrated superior activity and efficacy in clinical trials. ^{1 2 3 4 5}

What safety data exists for the combination therapy involving Cemiplimab, Gemcitabine, Motixafortide, and Nab paclitaxel?

Studies have shown that the combination of nab-paclitaxel and gemcitabine has an acceptable safety profile in patients with advanced pancreatic cancer and other solid tumors. This suggests that these drugs are generally safe for use in humans, although specific safety data for the exact combination therapy you mentioned may not be available. ^{6 7 8 9 10}

How is the combination therapy of Cemiplimab, Gemcitabine, and Nab paclitaxel unique for treating pancreatic cancer?

This combination therapy is unique because it includes Cemiplimab, an immunotherapy drug that helps the immune system fight cancer, alongside Gemcitabine and Nab paclitaxel, which have shown improved survival rates in pancreatic cancer patients compared to Gemcitabine alone. ^{1 3 5 11 12}

Research Team

Gulam A. Manji

Principal Investigator

Columbia University

Eligibility Criteria

Adults over 18 with stage IV pancreatic adenocarcinoma, not endocrine or acinar types, who haven't had recent major surgery or cancer treatments. They must have a good performance status and organ function, no severe allergies to study drugs, and agree to use birth control if applicable.

Inclusion Criteria

Ability to comply with study protocol according to investigator's judgement

My cancer is not endocrine or acinar pancreatic carcinoma.

My liver tests are normal or slightly elevated due to a blockage that can be treated.

Exclusion Criteria

I have skin conditions like eczema or psoriasis but only on my skin.

I have had surgery for pancreatic cancer.

History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Priming

Participants receive motixafortide daily for 5 days to prime the immune system

1 week

Treatment

Participants receive motixafortide twice a week, cemiplimab once every three weeks, and standard chemotherapy (gemcitabine and nab-paclitaxel)

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Cemiplimab
• Gemcitabine
• Motixafortide
• Nab paclitaxel

Trial Overview The trial tests a combination of chemotherapy (gemcitabine and nab-paclitaxel), immunotherapy (cemiplimab), and a chemokine inhibitor (motixafortide) for effectiveness in shrinking tumors, extending life, and safety in metastatic pancreatic cancer patients.

Participant Groups

Group I: Motixafortide, Cemiplimab, Gemcitabine, Nab-Paclitaxel Experimental Treatment 4 Interventions

Participants will receive standard FDA-approved doses of gemcitabine and nab-paclitaxel for pancreas cancer and cemiplimab at the dose that is approved for participants with skin cancer. Participants will also receive motixafortide at a dose that has been deemed safe in previous studies when used in combination with immunotherapy and chemotherapy. If the combination study treatment causes a serious side effect in participants, the study treatment will be modified.

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Gulam Manji

Lead Sponsor

Trials

5

Recruited

160+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

BioLine Rx

Collaborator

Trials

1

Recruited

10+

Findings from Research

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 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]

In a study of 41 patients with advanced pancreatic adenocarcinoma, the combination of Nab-paclitaxel and gemcitabine showed an overall response rate of 36.6%, with a median progression-free survival of 6.7 months and median overall survival of 10 months, indicating its efficacy as a first-line treatment.

The treatment was well tolerated, with no grade 4 toxicities reported; the most common grade 3 toxicities included neutropenia and thrombocytopenia, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. De Vita, F., Ventriglia, J., Febbraro, A., et al.[2023]

Gemcitabine has been established as a new standard treatment for pancreatic cancer, showing improved clinical benefits, time to progression, and survival compared to older treatments like 5-fluorouracil.

Combining gemcitabine with cisplatin has shown better tumor response and time to progression than gemcitabine alone, although its impact on overall survival is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of advanced pancreatic cancer: a comparative analysis of randomized trials. Heinemann, V.[2022]

In a subanalysis of the MPACT trial involving 63 Canadian patients with metastatic pancreatic cancer, nab-paclitaxel plus gemcitabine (nab-P + Gem) showed a median overall survival of 11.9 months compared to 7.1 months for gemcitabine alone, indicating that nab-P + Gem is an effective treatment option.

The safety profile of nab-P + Gem was manageable, with common grade ≥3 adverse events including neutropenia (22%), fatigue (34%), and neuropathy (25%), suggesting that while there are risks, the benefits in terms of efficacy are significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3 MPACT Trial. Tehfe, M., Dowden, S., Kennecke, H., et al.[2023]

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

In a study involving 866 patients with resected pancreatic ductal adenocarcinoma, the combination of nab-paclitaxel and gemcitabine showed a significant improvement in overall survival (OS) compared to gemcitabine alone, with a median OS of 41.8 months versus 37.7 months, respectively.

Although the primary endpoint of disease-free survival (DFS) was not significantly improved with nab-paclitaxel + gemcitabine, the treatment was associated with a higher incidence of grade ≥ 3 adverse events (86% vs. 68% for gemcitabine), indicating a need for careful consideration of safety alongside efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. Tempero, MA., Pelzer, U., O'Reilly, EM., et al.[2023]

The combination of APX005M (sotigalimab) with gemcitabine and nab-paclitaxel, with or without nivolumab, was found to be tolerable in patients with metastatic pancreatic adenocarcinoma, with a recommended phase 2 dose of 0.3 mg/kg for APX005M established during the study.

Clinical activity was observed, with 58% of patients showing responses, suggesting that this treatment regimen could potentially replace the current chemotherapy-only standard of care for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. O'Hara, MH., O'Reilly, EM., Varadhachary, G., et al.[2022]

In a phase I trial involving 50 patients with advanced pancreatic cancer, the combination of nivolumab, nab-paclitaxel, and gemcitabine showed a manageable safety profile, with 48 patients experiencing grade 3/4 treatment-emergent adverse events, but only one dose-limiting toxicity reported.

The treatment resulted in a median overall survival of 9.9 months and an overall response rate of 18%, indicating limited efficacy, which led to the conclusion that further investigation of this combination is not supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. Wainberg, ZA., Hochster, HS., Kim, EJ., et al.[2022]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

The introduction of nab-paclitaxel combined with gemcitabine has significantly improved survival rates for patients with advanced pancreatic cancer, as demonstrated in the MPACT study from 2013.

Prior to 2011, treatment options for pancreatic cancer were limited, primarily relying on gemcitabine, but the Phase III results of FOLFIRINOX and subsequent studies have expanded the therapeutic options available for oncologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel and gemcitabine for the treatment of patients with metastatic pancreatic cancer. Borazanci, E., Von Hoff, DD.[2022]

References

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. Germany pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. [2023]

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

Gemcitabine in the treatment of advanced pancreatic cancer: a comparative analysis of randomized trials. [2022]

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

nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3 MPACT Trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

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

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. [2022]

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

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. [2022]

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

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

11. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel and gemcitabine for the treatment of patients with metastatic pancreatic cancer. [2022]