Botensilimab + Chemotherapy for Pancreatic Cancer

Not currently recruiting at 37 trial locations

Overseen By Agenus, Inc. Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Agenus Inc.

Must not be taking: Corticosteroids, Immunosuppressives, others

Disqualifiers: CNS metastasis, Active infections, 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: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a new drug, botensilimab, to the usual chemotherapy treatment can help people with metastatic pancreatic cancer more effectively than chemotherapy alone. Participants will be divided into two groups: one will receive only the standard chemotherapy, while the other will receive botensilimab along with chemotherapy. The trial seeks participants with pancreatic cancer that has spread and who have already tried a specific chemotherapy regimen called FOLFIRINOX, which is no longer effective. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like cytotoxic agents, monoclonal antibodies, and small molecule therapies must be stopped within specific time frames before starting the study drugs.

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

Research has shown that combining the drug botensilimab with chemotherapy drugs gemcitabine and nab-paclitaxel was tested for safety in earlier studies. These studies assessed patient tolerance to this combination. Results suggested that most patients tolerated the treatment fairly well.

However, any new treatment can have side effects. Some past participants experienced side effects, but these were usually manageable. Since this clinical trial is in a later stage, it indicates that earlier trials demonstrated some level of safety. This is encouraging, but discussing potential risks and benefits with a healthcare provider before joining a clinical trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about botensilimab because, unlike the standard chemotherapy options for pancreatic cancer, it introduces a novel immune-enhancing approach. Most treatments, like nab-paclitaxel and gemcitabine, focus on directly attacking cancer cells. But botensilimab works differently, stimulating the immune system to recognize and fight the cancer more effectively. This unique mechanism could potentially improve outcomes by harnessing the body's natural defenses, offering new hope for patients with this challenging condition.

What evidence suggests that botensilimab plus chemotherapy might be an effective treatment for pancreatic cancer?

Research has shown that botensilimab, when combined with standard chemotherapy, may help treat pancreatic cancer. In this trial, participants in certain arms will receive botensilimab along with standard-of-care chemotherapy (nab-paclitaxel + gemcitabine). In a study involving patients previously treated with FOLFIRINOX (a type of chemotherapy), 80% of those who received botensilimab with chemotherapy experienced tumor shrinkage that persisted. Botensilimab aids the immune system in fighting cancer by enabling immune cells to more easily locate and attack tumors. This combination with chemotherapy could improve outcomes for people with advanced pancreatic cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Agenus Inc.

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic cancer who have already tried FOLFIRINOX treatment. They should be relatively healthy otherwise, with a life expectancy of at least 3 months and able to perform daily activities (ECOG status 0 or 1). Participants must not have other active cancers or serious illnesses, no history of severe allergies to study drugs, and agree to use effective contraception.

Inclusion Criteria

My diagnosis is pancreatic cancer confirmed by tissue analysis.

My organs are working well.

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

Exclusion Criteria

I have not received a COVID-19 vaccine in the week before starting the study drugs.

I have had more than one treatment for my metastatic disease.

I have been treated with drugs that boost the immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Participants receive botensilimab in combination with standard-of-care chemotherapy to establish safety and dose for Part 2

8 weeks

Treatment

Participants receive either botensilimab with chemotherapy or chemotherapy alone

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Botensilimab
• Gemcitabine
• Nab-paclitaxel

Trial Overview The study is testing the effectiveness of Botensilimab when added to standard chemotherapy (Gemcitabine and Nab-paclitaxel) versus chemotherapy alone in treating metastatic pancreatic cancer. Patients are divided into two groups: one receiving only chemotherapy and the other receiving both Botensilimab and chemotherapy.

How Is the Trial Designed?

Group I: Part 2: Combination Experimental Treatment 3 Interventions

Participants will receive botensilimab in combination standard-of-care chemotherapy (nab-paclitaxel + gemcitabine).

Group II: Part 1: Combination (Safety Lead-in Phase) Experimental Treatment 3 Interventions

Participants will receive botensilimab in combination with standard-of-care chemotherapy (nab-paclitaxel + gemcitabine).

Group III: Part 2: Standard of Care Active Control 2 Interventions

Participants will receive standard-of-care chemotherapy (nab-paclitaxel + gemcitabine).

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Agenus Inc.

Lead Sponsor

Trials

58

Recruited

4,900+

Published Research Related to This Trial

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

In a study using 10 patient-derived pancreatic cancer xenograft mouse models, the combination of S-1 and nab-paclitaxel showed significantly greater tumor growth inhibition (103.56%) compared to either treatment alone, indicating enhanced antitumor activity.

Biomarkers such as thymidylate synthase, OPRT, and DPD were identified as potential predictors of S-1 efficacy, while HER2 was linked to improved efficacy of nab-paclitaxel, suggesting that these markers could help tailor treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-Paclitaxel Plus S-1 Shows Increased Antitumor Activity in Patient-Derived Pancreatic Cancer Xenograft Mouse Models. Li, JA., Xu, XF., Han, X., et al.[2017]

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 phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., et al.[2023]

In a study involving 221 patients with metastatic pancreatic ductal adenocarcinoma and poor performance status, the combination of NAB-paclitaxel and gemcitabine was found to be well tolerated, with manageable side effects such as anemia and neutropenia.

Both dosing regimens of NAB-paclitaxel (100 mg/m2 and 125 mg/m2) showed similar efficacy, with comparable response rates and median progression-free survival, indicating that this treatment is effective for fragile patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. Macarulla, T., Pazo-Cid, R., Guillén-Ponce, C., et al.[2022]

The recent phase III MPACT trial demonstrated that nab-paclitaxel, when added to gemcitabine, significantly improved survival rates in patients with metastatic pancreatic cancer, indicating its efficacy in a previously challenging area.

The success of nab-paclitaxel highlights the importance of innovative drug delivery technologies, such as albumin nanoparticle formulations, in enhancing the effectiveness of anticancer therapies while minimizing toxicities associated with traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. Ma, WW., Hidalgo, M.[2022]

Gemcitabine-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully developed and showed a favorable controlled release, with an encapsulation rate of approximately 83% and a particle size of about 150 nm.

In vivo studies demonstrated that Gem-HSA-NPs significantly inhibited tumor growth in pancreatic cancer while exhibiting lower toxicity compared to other treatment groups, indicating their potential as a safer and more effective delivery method for gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. Yu, X., Di, Y., Xie, C., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05630183

NCT05630183 | A Study of Botensilimab in Participants ... The goal of this clinical trial is to test if the addition of botensilimab to standard chemotherapy improves the efficacy compared to just ...

2. investor.agenusbio.com investor.agenusbio.com/news/news-details/2023/Agenus-Unveils-New-and-Updated-Botensilimab-Data-in-Colorectal-Pancreatic-Lung-Melanoma-and-Sarcoma/default.aspx

Agenus Unveils New and Updated Botensilimab Data in ... In FOLFIRINOX relapsed/refractory (2L) pancreatic cancer, 80% of evaluable patients (n=5; 150mg BOT+gem-Abraxane) experienced sustained tumor ...

3. letswinpc.org letswinpc.org/research/new-immunotherapy-metastatic-pancreatic-cancer/

New Immunotherapy Metastatic Pancreatic Cancer A new drug, botensilimab, has been designed to optimize the interactions between cancer-fighting immune T cells and the antigens that alert the immune system ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609826/

Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is ... Botensilimab Effectively Treats Multiple Human Cancers. We have previously reported clinical results from an ongoing expanded phase I trial ( ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.LBA8

Results from a phase 1a/1b study of botensilimab (BOT) ... In heavily pretreated metastatic MSS CRC pts, BOT + BAL continues to demonstrate promising clinical activity with durable responses and was well tolerated.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05630183

NCT05630183 | A Study of Botensilimab in Participants ... The goal of this clinical trial is to test if the addition of botensilimab to standard chemotherapy improves the efficacy compared to just chemotherapy ...

7. jcto.weill.cornell.edu jcto.weill.cornell.edu/open_clinical_trials/a-randomized-open-label-phase-ii-trial-of-nab-paclitaxel-gemcitabine-with-or-without-botensilimab-agen1181-in-patients-with-metastatic-pancreatic-cancer-who-have-progressed-on-prior-5fu-leucovorin-irinotecan-oxaliplatin-folfirinox

A Randomized, Open-Label, Phase II Trial of Nab ... The purpose of this study is to determine the safety and effectiveness of a new study drug called botensilimab (AGEN1811) when given in combination with the ...

8. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-ii-randomized-open-label-trial-nab-paclitaxel-gemcitabine-or-without-botensilimab-agen1181-patients-metastatic-pancreatic-cancer-who-have-progressed-prior-5fu-leucovorin-irinotecan-oxaliplatin

A PHASE II RANDOMIZED, OPEN-LABEL, TRIAL OF NAB ... The purpose of this study is to find out if study drug, botensilimab, when given in combination with chemotherapy consisting of nab-paclitaxel + gemcitabine ...

9. clinicaltrials.ucbraid.org clinicaltrials.ucbraid.org/trial/NCT05630183

Botensilimab in Participants With Metastatic Pancreatic Cancer This will be a prospective, multicenter, clinical trial of botensilimab in combination with nab-paclitaxel + gemcitabine or nab-paclitaxel + ...