KRAS Vaccine Combo for Colorectal and Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Nilofer Azad, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disease, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Phase 1b study evaluating the efficacy and immune response to a synthetic long peptide mutant KRAS vaccine (SPL mKRASvax) combined with Balstilimab and Botensilimab for unresectable or metastatic mismatch repair-proficient (MMR-p) colorectal cancer (mCRC) or unresectable or metastatic MMR-p pancreatic ductal adenocarcinoma (PDAC) patients with measurable disease following first-line FOLFIRINOX/FOLFOXIRI (FFX).

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 active immunosuppressive agents or chronic systemic corticosteroids within 14 days of the vaccine treatment.

What data supports the effectiveness of the KRAS Vaccine Combo treatment for colorectal and pancreatic cancer?

Research shows that vaccines targeting KRAS mutations, which are common in pancreatic cancer, can trigger strong immune responses and have shown promising results in early studies. Additionally, dendritic cell-based vaccines have been effective in reducing tumor growth and increasing survival in pancreatic cancer models, suggesting potential benefits when combined with other treatments. ^{1 2 3 4 5}

Is the KRAS Vaccine Combo generally safe for humans?

The safety of treatments like the KRAS Vaccine Combo, which includes immune checkpoint inhibitors, has been studied in various cancers. These treatments can cause immune-related side effects, but the specific safety profile for the KRAS Vaccine Combo in colorectal and pancreatic cancer is not detailed in the available research. ^{6 7 8 9 10}

What makes the KRAS Vaccine Combo treatment unique for colorectal and pancreatic cancer?

The KRAS Vaccine Combo treatment is unique because it targets specific mutations in the KRAS gene, which are common in colorectal and pancreatic cancers, using a vaccine approach combined with immune checkpoint inhibitors. This combination aims to enhance the body's immune response against the cancer, potentially overcoming the limitations of current treatments that have limited efficacy in these cancers. ^{2 3 4 11 12}

Eligibility Criteria

This trial is for patients with stage IV MMR-p colorectal or pancreatic ductal cancer who have measurable disease after first-line FOLFIRINOX/FOLFOXIRI treatment. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

I am using an approved method of birth control.

Ability to understand and sign a written informed consent document

My cancer tissue is available for advanced genetic testing.

Exclusion Criteria

I am eligible for surgery to remove my cancer.

I have not needed treatment for an autoimmune disease in the last 5 years.

I have fluid buildup in my chest or abdomen.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the synthetic long peptide mutant KRAS vaccine (SPL mKRASvax) combined with Balstilimab and Botensilimab

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Extension

Participants may continue to be monitored for progression-free survival and other outcomes

3 years

Treatment Details

Interventions

• Balstilimab (Monoclonal Antibodies)
• Botensilimab (Monoclonal Antibodies)
• KRAS Vaccine with Poly-ICLC adjuvant (Cancer Vaccine)

Trial Overview The study is testing a new KRAS vaccine combined with two immunotherapy drugs: Balstilimab and Botensilimab. It's in phase 1 to see how effective this combo is against certain types of advanced colorectal and pancreatic cancers.

Participant Groups

Group I: SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab Experimental Treatment 3 Interventions

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Sidney Kimmel Comprehensive Cancer Center Baltimore, MD

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Lead Sponsor

Agenus Inc. Industry Sponsor

Private Philanthropic Funds Collaborator

National Institutes of Health (NIH) Collaborator

References

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

Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer. [2023] Label="PURPOSE">Two studies in previously treated metastatic pancreatic cancer have been completed combining GVAX pancreas vaccine (GM-CSF-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes-expressing mesothelin). In the current study, we compared Cy/GVAX followed by CRS-207 with (Arm A) or without nivolumab (Arm B).

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

Dendritic cell-based vaccination: powerful resources of immature dendritic cells against pancreatic adenocarcinoma. [2021] Pancreatic adenocarcinoma (PAC) has a poor prognosis. One treatment approach, investigated here, is to reinforce antitumor immunity. Dendritic cells (DCs) are essential for the development and regulation of adaptive host immune responses against tumors. A major role for DCs may be as innate tumoricidal effector cells. We explored the efficacy of vaccination with immature (i)DCs, after selecting optimal conditions for generating immunostimulatory iDCs. We used two models, C57BL/6Jrj mice with ectopic tumors induced by the PAC cell line, Panc02, and genetically engineered (KIC) mice developing PAC. Therapeutic iDC-vaccination resulted in a significant reduction in tumor growth in C57BL/6Jrj mice and prolonged survival in KIC mice. Prophylactic iDC-vaccination prevented subcutaneous tumor development. These protective effects were long-lasting in Panc02-induced tumor development, but not in melanoma. iDC-vaccination impacted the immune status of the hosts by greatly increasing the percentage of CD8+ T-cells, and natural killer (NK)1.1+ cells, that express granzyme B associated with Lamp-1 and IFN-γ. Efficacy of iDC-vaccination was CD8+ T-cell-dependent but NK1.1+ cell-independent. We demonstrated the ability of DCs to produce peroxynitrites and to kill tumor cells; this killing activity involved peroxynitrites. Altogether, these findings make killer DCs the pivotal actors in the beneficial clinical outcome that accompanies antitumor immune responses. We asked whether efficacy can be improved by combining DC-vaccination with the FOLFIRINOX regimen. Combined treatment significantly increased the lifespan of KIC mice with PAC. Prolonged treatment with FOLFIRINOX clearly augmented this beneficial effect. Combining iDC-vaccination with FOLFIRINOX may therefore represent a promising therapeutic option for patients with PAC.

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

Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine. [2020] Codon 12 mutations of K-ras are frequent in pancreatic adenocarcinoma, and represent potential tumor-specific neoantigens. The objective of this study was to assess the safety and efficacy of immunizing patients with resected pancreatic cancer with a vaccine targeted against their tumor-specific K-ras mutation.

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

Cancer vaccines: Targeting KRAS-driven cancers. [2021] Introduction: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers.Areas covered: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers.Expert opinion: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.

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

The immunotherapeutic effect of dendritic cells vaccine modified with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma. [2019] To estimate the effect of a therapeutic vaccine against pancreatic carcinoma based on dendritic cell (DC) vaccine modified with tumor lysate and Interleukin-18 gene.

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

Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis. [2023] This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.

7. England pubmed.ncbi.nlm.nih.gov

Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors. [2023] Whether influenza vaccination (FV) is associated with the severity of immune-related adverse events (IRAEs) in patients with advanced thoracic cancer on immune checkpoint inhibitors (ICIs) is not fully understood.

8. China pubmed.ncbi.nlm.nih.gov

Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events. [2021] We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events (irAEs) as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors (ICIs) in patients with advanced pan-cancer in a real-world setting.

9. Germany pubmed.ncbi.nlm.nih.gov

Predictors of immune checkpoint inhibitor-related adverse events in older patients with lung cancer: a prospective real-world analysis. [2023] Older patients with cancer are underrepresented in pivotal trials of immune checkpoint inhibitors (ICIs). This study aimed to investigate immune-related adverse events (irAEs) that occur in older patients with lung cancer treated with ICIs, and explore predictors of the occurrence of irAEs.

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

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. [2022] With the increased use of immune checkpoint inhibitors (ICIs) in advanced lung cancer, adverse events (AEs), particularly immune-related AEs (irAEs), have garnered considerable interest. We conducted a comprehensive assessment of the toxicity profile in advanced lung cancer using multi-source medical data.

11. England pubmed.ncbi.nlm.nih.gov

Vaccines and immune checkpoint inhibitors: a promising combination strategy in gastrointestinal cancers. [2022] Tweetable abstract US FDA-approved immune checkpoint inhibitors have limited efficacy for gastrointestinal cancers such as #colorectalcancer and #pancreaticcancer. Could combinations with experimental cancer 'vaccines' be the key?

12. Egypt pubmed.ncbi.nlm.nih.gov

The therapeutic effect of cytokine-induced killer cells on pancreatic cancer enhanced by dendritic cells pulsed with K-ras mutant peptide. [2021] This study is to investigate the role of the CIKs cocultured with K-ras-DCs in killing of pancreatic cancer cell lines, PANC-1 (K-ras(+)) and SW1990 (K-ras(-)).