Autogene Cevumeran + Atezolizumab + Chemotherapy for Pancreatic Cancer

(IMCODE003 Trial)

Recruiting at 88 trial locations

Overseen By Reference Study ID Number: GO44479 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genentech, Inc.

Must not be taking: Brivudine, Sorivudine, CYP3A4 inhibitors

Disqualifiers: Prior treatment, Autoimmune disease, Pregnancy, 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)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 weeks

260 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications, such as brivudine, sorivudine, or their related drugs, within 4 weeks before starting the study. Also, you cannot be on strong inhibitors or inducers of specific liver enzymes (CYP3A4 and UGT1A1).

What data supports the effectiveness of the treatment Autogene Cevumeran + Atezolizumab + Chemotherapy for Pancreatic Cancer?

Research shows that modified FOLFIRINOX, a part of this treatment, improves safety and survival in patients with advanced pancreatic cancer, making it a promising option for those who cannot undergo surgery. ^{1 2 3 4 5}

What safety data exists for the treatment combination of Autogene Cevumeran, Atezolizumab, and Chemotherapy for Pancreatic Cancer?

The modified FOLFIRINOX (mFOLFIRINOX) chemotherapy regimen, which is part of the treatment, has been associated with significant side effects, including diarrhea, fatigue, nausea, vomiting, and serious blood-related issues like neutropenia (low white blood cell count). However, modifications to the regimen may reduce these adverse effects and improve treatment tolerance. ^{1 6 7 8 9}

How is the treatment with Autogene Cevumeran + Atezolizumab + Chemotherapy for Pancreatic Cancer different from other treatments?

This treatment combines a personalized cancer vaccine (Autogene Cevumeran) and an immune checkpoint inhibitor (Atezolizumab) with chemotherapy, which is unique because it aims to boost the body's immune response against cancer cells while using standard chemotherapy to attack the cancer directly. This approach is different from traditional treatments that typically rely solely on chemotherapy or other single-modality therapies. ^{10 11 12 13 14}

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of adjuvant autogene cevumeran plus atezolizumab and modified leucovorin, 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (mFOLFIRINOX) versus mFOLFIRINOX alone in participants with resected pancreatic ductal adenocarcinoma (PDAC) who have not received prior systemic anti-cancer treatment for PDAC and have no evidence of disease after surgery.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with resected pancreatic ductal adenocarcinoma who haven't had prior cancer treatments and show no signs of disease post-surgery. They must have certain pathology stages, recovered from surgery, normal organ function, and agree to contraception.

Inclusion Criteria

Female participants of childbearing potential must be willing to avoid pregnancy during the treatment period and for 90 days after the final dose of autogene cevumeran, for 6 months after the last dose of chemotherapy, and for 5 months after the final dose of atezolizumab

My diagnosis of pancreatic cancer is confirmed through tissue examination.

It has been 6 to 12 weeks since my pancreatic cancer surgery.

Exclusion Criteria

I have had initial treatment for pancreatic cancer.

Pregnancy or breastfeeding

I do not have a spleen and have not had a distal pancreatectomy with splenectomy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either autogene cevumeran plus atezolizumab and mFOLFIRINOX or mFOLFIRINOX alone

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Atezolizumab
• Autogene cevumeran
• mFOLFIRINOX

Trial Overview The study tests the effectiveness and safety of adding autogene cevumeran and atezolizumab to mFOLFIRINOX chemotherapy compared to mFOLFIRINOX alone in patients after surgical removal of pancreatic cancer.

Participant Groups

Group I: Arm 1: Autogene Cevumeran + Atezolizumab + mFOLFIRINOX Experimental Treatment 3 Interventions

Participants will receive autogene cevumeran, atezolizumab and mFOLFIRINOX.

Group II: Arm 2: mFOLFIRINOX Active Control 1 Intervention

Participants will receive mFOLFIRINOX.

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

Approved in European Union as mFOLFIRINOX for:

• Pancreatic ductal adenocarcinoma (PDAC)

Approved in United States as mFOLFIRINOX for:

• Advanced pancreatic cancer

Approved in Canada as mFOLFIRINOX for:

• Resectable pancreatic ductal adenocarcinoma

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

BioNTech SE

Industry 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

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]

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 phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., et al.[2020]

Modified-FOLFIRINOX (mFOLFIRINOX) significantly improves safety and tolerability for Chinese patients with locally advanced pancreatic cancer (LAPC), with a response rate of 37.1% and common severe side effects including neutropenia and anemia.

Patients with LAPC who received neoadjuvant therapy with mFOLFIRINOX and subsequently underwent surgery had a median overall survival of 27.7 months, which is significantly better than the 8.9 months seen in patients who had upfront surgery without prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Li, X., Guo, C., Li, Q., et al.[2023]

In a study of 74 patients with unresectable pancreatic cancer, modified FOLFIRINOX (mFOLFIRINOX) showed a tendency for improved overall survival (10.6 months) compared to sequential chemotherapy (8.5 months), although the difference was not statistically significant.

However, mFOLFIRINOX was associated with a higher incidence of severe adverse events (grade ≥3), such as neutropenia (40.9% vs. 3.3% in sequential chemotherapy), suggesting that sequential chemotherapy may offer a better risk-benefit balance for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX versus sequential chemotherapy (FOLFIRI/FOLFOX) as a second-line treatment regimen for unresectable pancreatic cancer: A real-world analysis. Tezuka, S., Ueno, M., Oishi, R., et al.[2023]

The modified FOLFIRINOX (mFOLFIRINOX) regimen showed a tolerable safety profile with lower hematological toxicity compared to the full-dose FOLFIRINOX, while still maintaining comparable efficacy in treating advanced pancreatic ductal adenocarcinoma (PDAC).

In a study of 18 patients, 80% achieved at least stable disease, with a median overall survival of 9.3 months and progression-free survival of 7.2 months, indicating that mFOLFIRINOX can be an effective treatment option for fit patients with advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Ghorani, E., Wong, HH., Hewitt, C., et al.[2023]

Modified FOLFIRINOX shows similar effectiveness in treating metastatic pancreatic adenocarcinoma (MPA) compared to standard FOLFIRINOX, with no significant differences in overall survival or progression-free survival among patients.

While modified FOLFIRINOX had a lower dose reduction rate, it was associated with a slightly higher incidence of severe toxicity, indicating that patient selection may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma. de Jesus, VHF., Camandaroba, MPG., Donadio, MDS., et al.[2023]

In the NIVACOR trial, a phase II study involving 10 patients with metastatic colorectal cancer, the combination of nivolumab with FOLFOXIRI/bevacizumab was found to be well tolerated, with no treatment-related deaths reported.

While 70% of patients experienced adverse events primarily related to the chemotherapy regimen, the overall toxicity profile was considered acceptable, indicating potential for further investigation in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI/Bevacizumab Plus Nivolumab as First-Line Treatment in Metastatic Colorectal Cancer RAS/BRAF Mutated: Safety Run-In of Phase II NIVACOR Trial. Damato, A., Bergamo, F., Antonuzzo, L., et al.[2022]

In a multicenter phase II study involving 31 chemotherapy-naïve Japanese patients with advanced pancreatic cancer, the modified FOLFIRINOX (mFX) regimen showed a response rate of 38.7% and a median overall survival of 14.9 months, indicating its efficacy as a first-line treatment.

While mFX resulted in fewer Grade 3 or 4 non-hematological adverse events compared to the standard FOLFIRINOX regimen, it still had a high incidence of hematological adverse events, particularly neutropenia (83.9%), suggesting the need for further optimization to enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. Yoshida, K., Iwashita, T., Uemura, S., et al.[2022]

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]

A nomogram was developed to predict 6-month survival in patients with metastatic and locally advanced pancreatic cancer treated with FOLFIRINOX, based on four key prognostic factors: performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio.

The nomogram demonstrated good accuracy in predicting outcomes, with a C index of 0.762 in an independent validation cohort, helping to identify patient subsets with varying prognoses based on the number of poor prognostic features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan. Fornaro, L., Leone, F., Vienot, A., et al.[2020]

The modified FOLFIRINOX regimen is effective and well-tolerated for patients with advanced nonmetastatic pancreatic cancer, showing a high rate of surgical resection (72% attempted, 51.1% accomplished) with manageable toxicity, primarily diarrhea in 14% of patients.

Patients who underwent surgical resection after treatment with mFOLFIRINOX experienced a median progression-free survival of 18 months, significantly longer than the 8 months for those who did not have surgery, indicating a potential survival benefit from this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Blazer, M., Wu, C., Goldberg, RM., et al.[2022]

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 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]

References

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

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

2. 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]

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

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. [2020]

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

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. [2023]

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

Modified FOLFIRINOX versus sequential chemotherapy (FOLFIRI/FOLFOX) as a second-line treatment regimen for unresectable pancreatic cancer: A real-world analysis. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]

7. China pubmed.ncbi.nlm.nih.gov

Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

FOLFOXIRI/Bevacizumab Plus Nivolumab as First-Line Treatment in Metastatic Colorectal Cancer RAS/BRAF Mutated: Safety Run-In of Phase II NIVACOR Trial. [2022]

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

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. [2022]

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

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

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

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan. [2020]

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

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. [2022]

13. England pubmed.ncbi.nlm.nih.gov

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

14. 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]