Neoantigen Vaccine + Pembrolizumab for Follicular Lymphoma

Overseen By Oriol Olive Noguer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must be taking: Rituximab

Must not be taking: Immunosuppressants, Immunomodulators

Disqualifiers: Autoimmune disease, Active infection, 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

Compensation: Varies

Number of Visits: 8

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain investigational agents or high doses of corticosteroids, and you should not have received a non-oncology vaccine within 2 weeks before starting the trial.

What data supports the effectiveness of the drug Pembrolizumab for treating Follicular Lymphoma?

Research shows that Pembrolizumab, when used in combination with other treatments, has shown promise in treating various types of cancers, including non-small-cell lung cancer and certain lymphomas. It has demonstrated the ability to improve survival rates and induce specific immune responses, suggesting potential effectiveness in similar conditions. ^{1 2 3 4 5}

Is the combination of Neoantigen Vaccine and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in cancer treatment and is generally considered safe, but it can cause some side effects. These include rare cases of type 1 diabetes (a condition where the body can't produce insulin) and pneumonitis (inflammation of the lungs), which occurs in 1%-5% of patients. Other common side effects include fatigue, cough, nausea, and skin rash. ^{6 7 8 9 10}

How is the treatment with Neoantigen Vaccine and Pembrolizumab unique for follicular lymphoma?

This treatment is unique because it combines a personalized neoantigen vaccine, which is tailored to the specific mutations in a patient's tumor, with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This personalized approach aims to enhance the body's immune response specifically against the cancer, potentially offering a more targeted and effective treatment option. ^{1 2 3 11 12}

What is the purpose of this trial?

This research study is studying a novel type of FL vaccine as a possible treatment for follicular lymphoma (FL). The agents involved in this study are: * Rituximab * Personalized NeoAntigen vaccine * Poly-ICLC * Pembrolizumab

Research Team

Reid W Merryman, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with grade I-IIIA follicular lymphoma who haven't had systemic therapy except rituximab. They must have measurable disease, normal organ/marrow function, and be willing to provide tissue samples for research. Women of childbearing potential and men must agree to use contraception.

Inclusion Criteria

Ability to understand and sign a written informed consent document

Patient must have measurable disease by Cheson criteria

I agree to provide samples of my tumor and normal tissues for testing.

Exclusion Criteria

Underlying medical, psychiatric, or social conditions compromising study administration or AE assessment

I am HIV-positive and may be on antiretroviral therapy.

Active autoimmune disease or immunosuppressive conditions

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Rituximab Treatment

Participants receive 4 weekly doses of rituximab during NeoVax manufacturing

4 weeks

4 visits (in-person)

NeoVax and Pembrolizumab Treatment

Participants receive NeoVax alone or in combination with pembrolizumab, with injections at multiple timepoints

22 weeks

Multiple visits (in-person) on days 4, 8, 15, 22, 78, and 134

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Pembrolizumab
• Personalized NeoAntigen vaccine
• Rituximab

Trial Overview The study tests a new vaccine (NeoVax) alongside Pembrolizumab after initial treatment with Rituximab in patients with follicular lymphoma. The goal is to see if this combination can improve outcomes compared to current treatments.

Participant Groups

Group I: NeoVax and pembrolizumab Experimental Treatment 3 Interventions

* Neo Vax is injected into up to 4 different anatomic site. * NeoVax may be administered within +/- 1 day of the scheduled administration date for days 4 and 8, * Within +/-3 days of the scheduled administration date for days 15 and 22 * Within +/-7 days of days 78 and 134. * Patients will receive pembrolizumab every 3 weeks starting on day 78 * Participants will receive Rituximab weekly x 4 weeks per institutional standard

Group II: Neo Vax Experimental Treatment 2 Interventions

* Neo Vax is injected into up to 4 different anatomic site. * NeoVax may be administered within +/- 1 day of the scheduled administration date for days 4 and 8, * Within +/-3 days of the scheduled administration date for days 15 and 22 * Within +/-7 days of days 78 and 134. * Participants will receive Rituximab weekly x 4 weeks per institutional standard

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

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Findings from Research

The phase 1b clinical trial showed that the combination of the personalized vaccine NEO-PV-01 with chemotherapy and the anti-PD-1 drug pembrolizumab was well tolerated in patients with first-line metastatic non-squamous NSCLC.

This treatment regimen successfully induced specific CD4+ T cell responses targeting neoantigens, suggesting a promising mechanism for enhancing the immune response against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining personalized neoantigen vaccination with chemotherapy and anti-PD-1 to treat NSCLC. Leung, CSK., Van den Eynde, BJ.[2022]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., et al.[2023]

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]

Pembrolizumab, an immunotherapy for advanced non-small-cell lung cancer (NSCLC), significantly improves progression-free and overall survival compared to traditional chemotherapy, with fewer side effects, particularly in patients with high PD-L1 expression (≥50%).

In combination with pemetrexed and carboplatin, pembrolizumab also enhances treatment effectiveness and maintains manageable toxicity, leading to a shift in first-line treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Reck, M.[2018]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant clinical efficacy in treating Hodgkin Lymphoma and promising early results in certain subtypes of Non-Hodgkin Lymphoma, particularly those with genetic similarities to HL.

Current data suggest that pembrolizumab has a favorable safety profile and efficacy as a single agent in treating diffuse large B cell lymphomas, with future strategies likely to focus on biomarker-driven approaches and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. Sheikh, S., Kuruvilla, J.[2020]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In patients with relapsed and refractory classical Hodgkin's lymphoma who have previously failed treatment with brentuximab vedotin, pembrolizumab significantly improves progression-free survival (PFS) compared to standard of care, with hazard ratios indicating a much lower risk of disease progression.

The study involved a systematic literature review and comparisons of outcomes from pembrolizumab's KEYNOTE-087 trial against an observational study of standard care, confirming that pembrolizumab is a more effective treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. Keeping, S., Wu, E., Chan, K., et al.[2019]

References

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

Combining personalized neoantigen vaccination with chemotherapy and anti-PD-1 to treat NSCLC. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]

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

Personalized Vaccine Induces Antitumor Activity. [2021]

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

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. [2018]

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

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

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

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. [2019]

12. Croatia pubmed.ncbi.nlm.nih.gov

PERSONALIZED NEOANTIGEN VACCINE AGAINST CANCER. [2021]