mFOLFIRINOX + BNT321 for Pancreatic Cancer

Recruiting at 3 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must be taking: mFOLFIRINOX

Must not be taking: Antiinfectives, Antivirals

Disqualifiers: Pregnancy, Active cancer, Infections, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

2 Participants Needed

Trial Summary

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 should discuss your current medications with the trial investigators to ensure they don't interfere with the trial treatments.

What data supports the idea that mFOLFIRINOX + BNT321 for Pancreatic Cancer is an effective treatment?

The available research shows that modified FOLFIRINOX (mFOLFIRINOX) is effective for treating advanced pancreatic cancer. In a study, the 6-month and 1-year survival rates for patients with locally advanced pancreatic cancer were 90.9% and 76.2%, respectively. For metastatic pancreatic cancer, the rates were 79.7% and 47.6%. Additionally, the treatment had a disease control rate of 76.7%, meaning most patients experienced some benefit. Compared to the standard dose, mFOLFIRINOX has fewer side effects, making it a more tolerable option for patients. ^{1 2 3 4 5}

What safety data is available for mFOLFIRINOX and BNT321 in treating pancreatic cancer?

The safety data for mFOLFIRINOX shows that it is a modified version of the standard FOLFIRINOX regimen, designed to reduce toxicity while maintaining efficacy. Studies indicate that mFOLFIRINOX is generally better tolerated than the standard regimen, with common adverse events including neutropenia, thrombocytopenia, fatigue, nausea, vomiting, and diarrhea. Grade 3/4 adverse events are reported, but no chemotherapy-induced deaths were documented. The safety of BNT321 in combination with mFOLFIRINOX specifically is not detailed in the provided studies, suggesting that further research may be needed to fully understand the safety profile of this combination treatment. ^{1 2 3 6 7}

Is mFOLFIRINOX + BNT321 a promising drug for pancreatic cancer?

Yes, mFOLFIRINOX is a promising drug for pancreatic cancer. It is a modified version of a chemotherapy regimen that has shown to be effective and better tolerated, leading to improved survival rates in patients with advanced pancreatic cancer. ^{1 2 3 4 6}

What is the purpose of this trial?

This trial is designed as a Phase I/randomized Phase II open-label trial of modified(m) FOLFIRINOX ± BNT321 for adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC) patients post R0 or R1 resection. The Phase I, dose escalation part of this trial will be a limited evaluation of two planned BNT321 dose levels in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks). Following determination of the combination recommended Phase II dose (RP2D), the Phase II (randomized treatment) part of this trial will be initiated as an open-label 2-arm evaluation of mFOLFIRINOX ± BNT321 (24 weeks) followed by BNT321 monotherapy (24 weeks) in the combination arm only to complete the adjuvant therapy course. Treatment cycles are every 2 weeks (14 days).

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

Adults with confirmed pancreatic ductal adenocarcinoma who've had a complete tumor removal surgery can join this trial. They must have no metastatic disease, be fully recovered from surgery to start chemotherapy, and agree to use effective contraception. Exclusions include pregnancy, major recent surgery, significant heart risks, certain infections or allergies, other active cancers needing treatment soon.

Inclusion Criteria

Has signed an informed consent form (ICF) before initiation of any trial-specific procedures

My pancreatic cancer diagnosis was confirmed through lab tests.

Your lab test results are normal.

Exclusion Criteria

You have had a severe allergic reaction to a specific type of antibody.

Your blood test showed high levels of CA19-9 within 3 weeks before the start of the trial.

My surgery did not remove all of my tumor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation of BNT321 in combination with mFOLFIRINOX chemotherapy

24 weeks

Bi-weekly visits for treatment cycles

Phase I BNT321 Monotherapy

BNT321 monotherapy following combination treatment

24 weeks

Bi-weekly visits for treatment cycles

Phase II Treatment

Randomized treatment with mFOLFIRINOX ± BNT321

24 weeks

Bi-weekly visits for treatment cycles

Phase II BNT321 Monotherapy

BNT321 monotherapy in the combination arm

24 weeks

Bi-weekly visits for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 60 months

Treatment Details

Interventions

• BNT321 Dose Level 1
• BNT321 Dose Level 2
• BNT321 RP2D
• mFOLFIRINOX

Trial Overview The study tests the safety and effectiveness of mFOLFIRINOX alone or combined with varying doses of BNT321 as post-surgery therapy for pancreatic cancer. It's in two parts: first determining safe dosage levels (Phase I), then comparing treatments (Phase II) over 48 weeks with cycles every two weeks.

Participant Groups

Group I: Phase 2 - BNT321 RP2D + mFOLFIRINOX Experimental Treatment 2 Interventions

BNT321 in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks)

Group II: Phase 1 - BNT321 Dose Level 2 + mFOLFIRINOX Experimental Treatment 2 Interventions

BNT321 in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks)

Group III: Phase 1 - BNT321 Dose Level 1 + mFOLFIRINOX Experimental Treatment 2 Interventions

BNT321 in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks)

Group IV: Phase 2 - mFOLFIRINOX Active Control 1 Intervention

mFOLFIRINOX chemotherapy (24 weeks) as monotherapy

Who Is Running the Clinical Trial?

BioNTech SE

Lead Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

Modified-dose FOLFIRINOX (mFOLFIRINOX) demonstrated comparable efficacy to standard-dose FOLFIRINOX (sFOLFIRINOX) in treating pancreatic cancer, with similar objective response rates and overall survival outcomes among 130 patients studied.

mFOLFIRINOX was associated with significantly lower rates of severe adverse events, such as neutropenia, anorexia, and diarrhea, suggesting it is a safer option for patients who may be concerned about toxicity while maintaining effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. Kang, H., Jo, JH., Lee, HS., et al.[2022]

In a study of 15 patients with advanced biliary tract cancer who had not responded to previous chemotherapy, the modified FOLFIRINOX (mFOLFIRINOX) regimen showed promising efficacy, with a 26.7% objective response rate and an 80% disease control rate.

The treatment was well-tolerated, with a median overall survival of 13.2 months and manageable side effects, primarily grade 3/4 neutropenia, indicating that mFOLFIRINOX could be a viable salvage therapy option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study. Ye, LF., Ren, C., Bai, L., et al.[2022]

The modified FOLFIRINOX (mFOLFIRINOX) regimen demonstrated a high treatment efficacy in patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC), achieving a response rate of 55.2% among 29 evaluable patients.

The treatment was well-tolerated, with only 9 patients experiencing grade 3 or 4 adverse effects, and no patients discontinued treatment due to side effects, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. Bai, X., Su, R., Ma, T., et al.[2018]

In a study of 198 patients with advanced pancreatic cancer, the SOXIRI chemotherapy regimen showed similar overall survival (12.1 months) and progression-free survival (6.5 months) compared to the standard mFOLFIRINOX regimen (11.2 months and 6.8 months, respectively), indicating comparable efficacy.

While both regimens had similar safety profiles, SOXIRI was associated with a higher incidence of anemia (41.4% vs. 24%), suggesting that while effective, it may have specific side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. Li, X., Huang, J., Wang, F., et al.[2023]

Modified FOLFIRINOX for advanced pancreatic cancer showed promising survival rates, with 6-month overall survival at 90.9% for locally advanced cases and 79.7% for metastatic cases, based on a meta-analysis of 11 studies involving 563 patients.

This modified regimen resulted in fewer severe adverse events compared to conventional FOLFIRINOX, suggesting it may be a safer and more tolerable option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis. Tong, H., Fan, Z., Liu, B., et al.[2022]

FOLFIRINOX therapy demonstrated effectiveness in treating metastatic pancreatic cancer, with a disease control rate of 77.8% among 18 patients treated between 2014 and 2017.

Despite its efficacy, the treatment was associated with significant toxicities, including a high incidence of Grade 3 or higher adverse events, particularly neutropenia, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Treatment Outcomes of FOLFIRINOX for Unresectable and Recurrent Pancreatic Cancer]. Sakamoto, T., Takeda, Y., Ohmura, Y., et al.[2018]

In a study of 71 patients with resected pancreatic carcinoma, the modified FOLFIRINOX (mFOLFIRINOX) regimen showed significantly better 3-year relapse-free survival (RFS) and overall survival (OS) compared to S-1 monochemotherapy, indicating its greater efficacy as an adjuvant treatment.

While mFOLFIRINOX was associated with more severe side effects such as thrombocytopenia, fatigue, and nausea/vomiting, the study concluded that with proper management of these adverse events, mFOLFIRINOX could be a superior option for improving survival outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Center Retrospective Study to Compare the Efficacy and Safety of Modified FOLFIRINOX with S-1 as Adjuvant Chemotherapy in 71 Patients with Resected Pancreatic Carcinoma. Yao, L., Tang, C., Feng, W., et al.[2023]

References

1. China pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. [2022]

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

Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[The Treatment Outcomes of FOLFIRINOX for Unresectable and Recurrent Pancreatic Cancer]. [2018]

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

A Single-Center Retrospective Study to Compare the Efficacy and Safety of Modified FOLFIRINOX with S-1 as Adjuvant Chemotherapy in 71 Patients with Resected Pancreatic Carcinoma. [2023]