Personalized Cancer Vaccine + PD-L1 Blocker for Pancreatic Cancer

Recruiting at 9 trial locations

Overseen By Eileen M O'Reilly, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Myelosuppressives

Disqualifiers: Pregnancy, Active infection, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Varies

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to evaluate the safety or treating pancreatic cancer with surgery to remove cancerour tissue, followed by atezolizumab, followed by a personalized cancer vaccine (PCV), and then with chemotherapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you cannot take certain immunosuppressive medications within 2 weeks before starting the study treatment. It's best to discuss your current medications with the study team.

Is the combination of Personalized Cancer Vaccine and PD-L1 Blocker safe for humans?

Atezolizumab, a PD-L1 blocker, has been studied for safety in various cancers, including melanoma and bladder cancer. It has a favorable safety profile, but like other immune therapies, it can cause immune-related side effects such as colitis (inflammation of the colon) and other gastrointestinal issues. These side effects are generally less common with PD-L1 blockers compared to other similar treatments. ^{1 2 3 4 5}

How is the treatment with Atezolizumab and a personalized cancer vaccine unique for pancreatic cancer?

This treatment is unique because it combines a personalized cancer vaccine with Atezolizumab, a PD-L1 blocker, to enhance the body's immune response specifically against the patient's tumor, potentially overcoming the limitations of standard immunotherapy by making the tumor more recognizable to the immune system. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Atezolizumab, Tecentriq, PCV for pancreatic cancer?

Research suggests that combining cancer vaccines with immune checkpoint blockers, like PD-L1 inhibitors, may help the immune system better recognize and attack pancreatic cancer cells. This approach has shown promise in other studies by potentially transforming tumors to be more responsive to immunotherapy. ^{7 8 9 11 12}

Who Is on the Research Team?

Vinod Balachandran, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with resectable pancreatic cancer, specifically adenocarcinoma, who haven't had prior treatments like chemotherapy or immunotherapy. They must be in good physical condition (ECOG 0-1), able to follow the study plan, and agree to use effective contraception. Excluded are those with other cancers under treatment, serious organ/system conditions, certain infections or immune disorders, recent major heart issues, allergies requiring steroids pre-treatment.

Inclusion Criteria

Able to comply with the study protocol, in the investigator's judgment

Tumors must be radiographically resectable, defined as: A clear fat plane around the celiac and superior mesenteric arteries, patent superior mesenteric and portal veins without primary tumor involvement, no encasement of the superior mesenteric vein or portal veins, no encasement of the superior mesenteric or hepatic arteries, no metastatic disease, no extra-regional nodal disease, subjects with histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1) will be selected for neoantigen vaccine creation, pancreatic cancer surgical staging: T 1-3, N0-2, M0 per AJCC 8th edition staging, performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status, subjects must not have had prior chemotherapy, radiation therapy, or immunotherapy for PDAC, subjects must be able to read, understand, and sign informed consent, women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study initiation, for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures that result in a failure rate of less than (<) 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab and for at least 90 days after the last dose of RO7198457, for men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom during the entire study period and up to 90 days after last administration of RO7198457, examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization and established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices, hormonal contraceptive methods must be supplemented by a barrier method plus spermicide, the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient, periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception

My pancreatic tumor can be removed surgically and looks like adenocarcinoma on scans.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply: prior neoadjuvant treatment or radiation therapy for PDAC, prior therapy with uPD-1 antibody or any other immune therapy, borderline resectable, locally unresectable or metastatic PDAC, pancreas tumor histology other than PDAC, pregnancy, breastfeeding, or intending to become pregnant during the study or within 90 days after the last dose of study treatment, life expectancy less than 12 weeks, inability to comply with study and/or follow-up procedures, any other malignancy for which the patient is undergoing active treatment which will be concurrent with the investigational agent in this study, patients with unresolved Clavien-Dindo >/= Grade 3 postoperative complications, active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, active tuberculosis, known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection or subjects receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications, known hypersensitivity or allergy to the active substance or to any of the excipients of RO7198457, atezolizumab, oxaliplatin, leucovorin, irinotecan, or fluorouracil, serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, history of connective tissue disorders, history of interstitial lung disease, history of the following within 6 months prior to RO7198457 administration: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysthythmia, or electrocardiogram (ECG) abnormality, history or autoimmune disease, patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible, patient with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible, patients type 2 diabetes mellitus may be eligible, patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only may be eligible provided that they meet specific conditions, treatment with systemic immunosuppressive medication within 2 weeks prior to RO7198457 administration, subjects with allergies to IV contrast agents requiring pretreatment with corticosteroids, history of idiopathic pulmonary fibrosis, pneumonitis, known primary immunodeficiencies, prior allogeneic bone marrow transplantation or prior solid organ transplantation, any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug, known clinically significant liver disease, previous splenectomy, administration of a live, attenuated vaccine within 4 weeks before RO7198457 administration or anticipation that such a live attenuated vaccine will be required during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo surgery to remove cancerous tissue

1-2 weeks

Treatment

Participants receive atezolizumab followed by a personalized cancer vaccine (PCV) and then chemotherapy

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• PCV

Trial Overview The trial is testing a sequence of treatments for pancreatic cancer: surgery to remove the tumor followed by atezolizumab (a PD-L1 blocker), then a personalized cancer vaccine (PCV) tailored to the patient's tumor specifics, and finally mFOLFIRINOX chemotherapy regimen.

How Is the Trial Designed?

Group I: Pancreatic Cancer Experimental Treatment 3 Interventions

Radiologically resectable primary pancreatic tumors

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Massachusetts Institute of Technology

Collaborator

Trials

104

Recruited

12,810,000+

Genentech, Inc.

Industry 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

Published Research Related to This Trial

The Rotterdam PancrEAtic Cancer Vaccination-2 trial is investigating the safety and tolerability of a combination treatment using dendritic cell vaccines and an anti-CD40 agonistic antibody in patients with advanced pancreatic cancer, with a focus on those who have not responded to standard chemotherapy.

This phase I trial will include 12 to 18 patients and aims to assess treatment-induced immune responses and tumor-specific effects, potentially offering a new immunotherapy approach for a disease with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial). Lau, SP., van 't Land, FR., van der Burg, SH., et al.[2023]

The study proposes that combining personalized cancer vaccines with PD-1 blockade therapy can enhance the immune response in pancreatic cancer patients, particularly those with non-inflamed tumors that typically resist treatment.

Using a vaccine platform with autologous dendritic cells loaded with personalized neoantigen peptides, along with the PD-1 antibody nivolumab, aims to improve tumor recognition and response to therapy, demonstrating feasibility in three pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma-A Proof of Antigen Discovery Feasibility in Three Patients. Bassani-Sternberg, M., Digklia, A., Huber, F., et al.[2023]

In a meta-analysis of clinical trials, PD-1 inhibitors (like nivolumab and pembrolizumab) were found to have a higher incidence of colitis compared to PD-L1 inhibitors (like atezolizumab and durvalumab), with rates of 1.49% for all grade colitis and 0.85% for grade 3-4 colitis.

The analysis indicated that the relative risk of developing colitis with PD-1 inhibitors was significantly higher (1.80 for all grade colitis and 2.52 for grade 3-4 colitis), suggesting that patients receiving PD-1 inhibitors may need closer monitoring for this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Risk of Colitis With Programmed Death 1 Versus Programmed Death Ligand 1 Inhibitors for the Treatment of Cancer. Miyashita, H., Mikami, T., Satoi, S., et al.[2021]

Atezolizumab, an anti-PD-L1 therapy, was well tolerated in a study of 45 patients with advanced melanoma, showing that most side effects were mild (grade 1/2) and no treatment-related deaths occurred.

The treatment resulted in a 30% overall response rate and a median overall survival of 23 months, with certain biomarkers like PD-L1 expression and tumor mutational burden linked to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Hamid, O., Molinero, L., Bolen, CR., et al.[2020]

Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]

A study analyzing 70,330 adverse events reported to the FDA found that immune checkpoint inhibitors (ICIs) significantly increase the risk of gastrointestinal (GI) toxicities, particularly colitis, hepatobiliary disorders, and pancreatitis, with colitis showing the highest reporting odds ratio of 17.2.

The risk of these GI adverse events was notably higher with anti-CTLA-4 treatments compared to anti-PD-1 and anti-PD-L1 therapies, and factors such as female gender and polytherapy were identified as strong risk factors for these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System. Bai, X., Jiang, S., Zhou, Y., et al.[2021]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

In a phase Ib trial, a personalized cancer vaccine combined with the PD-L1 inhibitor atezolizumab demonstrated the ability to induce specific T-cell responses against neoantigens in patients with solid cancers.

This combination therapy resulted in complete or partial tumor eradication in some patients, indicating its potential efficacy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized Vaccine Induces Antitumor Activity. [2021]

The neoantigen-targeted vaccine PancVAX, developed using whole-exome and RNA sequencing, effectively activated T cells against pancreatic cancer in mice, leading to temporary tumor regression.

When combined with checkpoint modulators (anti-PD-1 and OX40 antibodies), PancVAX not only enhanced tumor regression but also promoted T cell memory, suggesting a potential for long-lasting immunity against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer. Kinkead, HL., Hopkins, A., Lutz, E., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial). [2023]

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

Programmed Cell Death Ligand-1 (PD-L1) and CD8 Expression Profiling Identify an Immunologic Subtype of Pancreatic Ductal Adenocarcinomas with Favorable Survival. [2021]

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

Engagement of T Cell-Expressed PD-L1 Weakens Antitumor Immunity. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma-A Proof of Antigen Discovery Feasibility in Three Patients. [2023]

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

IFN-γ down-regulates the PD-1 expression and assist nivolumab in PD-1-blockade effect on CD8+ T-lymphocytes in pancreatic cancer. [2020]

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

Incidence and Risk of Colitis With Programmed Death 1 Versus Programmed Death Ligand 1 Inhibitors for the Treatment of Cancer. [2021]

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

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. [2020]

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

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System. [2021]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

Personalized Vaccine Induces Antitumor Activity. [2021]

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

Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer. [2022]