Combination Therapy for Pancreatic Cancer

Recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments to determine if they can reduce pancreatic cancer tumors, extend patient survival, and ensure safety. It combines standard chemotherapy drugs with the immunotherapy drug cemiplimab, which aids the immune system in fighting cancer, and a new drug, motixafortide, to enhance the immunotherapy's effect. Individuals with confirmed metastatic pancreatic cancer (cancer that has spread and cannot be removed) who have not received prior treatment might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that the combination of motixafortide, cemiplimab, gemcitabine, and nab-paclitaxel has been studied for safety. These studies found that patients generally tolerated the treatment well. In one small trial, 64% of patients responded positively without serious safety issues.

Cemiplimab, one of the drugs in this combination, has FDA approval for treating skin cancer, so its safety is well-established in that area. Motixafortide has also been tested with other cancer treatments and was considered safe in those studies.

However, motixafortide has not been tested with cemiplimab and the specific chemotherapy drugs gemcitabine and nab-paclitaxel together before this trial. This means there is less direct safety data for this exact combination. The trial's Phase 2 status indicates that early safety results were positive enough to continue testing with more patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination therapy for pancreatic cancer because it includes motixafortide, which is not commonly used in standard treatments. Unlike typical options like gemcitabine and nab-paclitaxel, this therapy adds motixafortide, which is believed to potentially enhance immune response and improve the effectiveness of chemotherapy. Additionally, cemiplimab, an immunotherapy drug usually used for skin cancer, is included to boost the body's natural defenses against cancer cells. This innovative approach could offer a more powerful attack on pancreatic cancer, providing hope for better outcomes.

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

In this trial, participants will receive a combination of motixafortide, cemiplimab, gemcitabine, and nab-paclitaxel. Research has shown that motixafortide, when combined with other treatments, yields promising results for pancreatic cancer. Specifically, one study showed that 64% of patients experienced tumor shrinkage, known as a partial response. Cemiplimab, already approved for treating skin cancer, has demonstrated the ability to shrink tumors and improve survival rates when combined with chemotherapy. Gemcitabine and nab-paclitaxel are standard treatments for pancreatic cancer and together can reduce the risk of cancer progression by 31%. This combination might be more effective than chemotherapy alone, offering hope for better outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Gulam A. Manji

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

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.

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

I have had surgery for pancreatic cancer.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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 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]

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]

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]

Citations

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Libtayo® (cemiplimab-rwlc) Longer-term Results in ... With up to three years of follow-up, results from the pivotal Phase 2 trial showed 46% of patients (95% CI: 39%-53%) experienced substantial tumor shrinkage ...

2. oncodaily.com oncodaily.com/drugs/cemiplimab-rwlc-libtayo

Cemiplimab-rwlc (Libtayo) Updates 2025: Uses in cancer, ... These findings confirm that cemiplimab combined with platinum-based chemotherapy significantly improves survival outcomes compared to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04543071

Study Details | NCT04543071 | Chemo4METPANC ... Cemiplimab is FDA approved for treatment of skin cancer but not for pancreas cancer. Participants will also receive Motixafortide, a new medication which has ...

4. biolinerx.com biolinerx.com/immunotherapy-for-pancreatic-cancer/

Immunotherapy for Pancreatic Cancer The study's primary endpoint is progression-free survival, and secondary objectives include safety, response rate, disease control rate, duration of clinical ...

5. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06790602

Cemiplimab Plus Gemcitabine in Patients With Metastatic ... In retrospective studies, immune checkpoint inhibitors in SWI/SNF altered pancreatic ductal adenocarcinoma resulted in improved tumor responses and longer ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4167

CheMo4METPANC The goal of this first-in-human study was to evaluate safety, radiologic response rate, and change in tumor microenvironment (TME) elicited by ...

7. ir.biolinerx.com ir.biolinerx.com/node/14136/pdf

BioLineRx Announces New Pilot Phase ... The pilot clinical trial of motixafortide, cemiplimab, gemcitabine and nab-paclitaxel (N=11) demonstrated an overall response rate (ORR) of 64% ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT499452

CheMo4METPANC The goal of this first-in-human study was to evaluate safety, radiologic response rate, and change in tumor microenvironment (TME) elicited by motixafortide ( ...

9. onclive.com onclive.com/view/first-line-motixafortide-plus-cemiplimab-chemotherapy-induces-responses-in-mpdac

First-Line Motixafortide Plus Cemiplimab/Chemotherapy ... Based on early efficacy and safety data, the phase 2 study was amended to be a randomized trial. 2 The ongoing, open-label, multicenter study is ...