PANDA-VAC + Pembrolizumab for Lung Cancer

(PANDA-VAC Trial)

Overseen By Caroline Babinec

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: PD-1 therapy

Must not be taking: Systemic corticosteroids, Immunosuppressive drugs

Disqualifiers: Active infection, CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new personalized vaccine called PANDA-VAC when combined with pembrolizumab, a medicine already used for treating certain cancers. The focus is on individuals with advanced squamous non-small cell lung cancer or squamous cell carcinoma of the head and neck. The trial examines whether these treatments can work together safely. It is suitable for those previously treated for these cancers who still have visible disease and are stable or experiencing non-threatening progression. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using systemic corticosteroids at doses of 10mg prednisone daily or higher, or other immunosuppressive medications, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab is generally safe, with studies finding that people can tolerate it well over long periods. Specifically, a five-year study found pembrolizumab safe for people with certain types of lung cancer, demonstrating long-term survival benefits without major safety issues.

PANDA-VAC is a newer treatment still under study. Early trials are examining its safety for people. Similar studies on vaccines like PANDA-VAC have shown promising results in treating lung cancer, but researchers are still collecting more detailed safety information.

In summary, pembrolizumab has a proven safety record, while PANDA-VAC is still under evaluation for safety. This trial aims to learn more about how these treatments work together and their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for lung cancer, which often include chemotherapy and targeted therapies, PANDA-VAC combined with pembrolizumab is a unique approach because it uses a therapeutic neoantigen vaccine. This vaccine aims to stimulate the immune system by targeting specific proteins found on cancer cells, potentially enhancing the body's ability to fight the tumor. Researchers are excited because this method could lead to a more personalized and effective treatment by harnessing the body's own defenses, while pembrolizumab, an immune checkpoint inhibitor, further supports this immune response by preventing cancer cells from evading immune detection. This combination could offer a new avenue for treating lung cancer, focusing on immune system activation rather than just attacking the cancer cells directly.

What evidence suggests that PANDA-VAC combined with pembrolizumab could be effective for advanced squamous non-small cell lung cancer or squamous cell carcinoma of head and neck?

This trial will evaluate the combination of PANDA-VAC with pembrolizumab for treating squamous cell non-small cell lung cancer (NSCLC). Research shows that using PANDA-VAC with pembrolizumab might enhance the immune system's ability to fight this type of lung cancer. Pembrolizumab, a well-known treatment, has effectively slowed cancer progression when combined with chemotherapy. For instance, it reduced the chance of cancer spreading or worsening by 48% compared to chemotherapy alone. Long-term studies also indicate that pembrolizumab can extend the lives of people with advanced lung cancer. PANDA-VAC is designed to work with pembrolizumab by further training the immune system to specifically attack cancer cells. While detailed human data on PANDA-VAC is still being gathered, the combination with pembrolizumab seems promising based on their synergistic action. ^{1 4 6 7 8}

Who Is on the Research Team?

Jared Weiss, MD

Principal Investigator

UNC Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults with advanced squamous non-small cell lung cancer or head and neck squamous cell carcinoma who have stable disease or limited progression on certain immune therapies. They must have good organ function, measurable disease, and be able to consent to biopsies. Pregnant women, those with autoimmune diseases requiring treatment in the past 2 years, active infections, or other cancers needing treatment are excluded.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

I agree to a biopsy for vaccine study if my cancer shows certain responses after 7 vaccinations.

My cancer hasn't worsened significantly on my current immunotherapy treatment.

Exclusion Criteria

I am currently being treated for an infection.

My doctor thinks pembrolizumab and PANDA-VAC are not suitable for me.

You have a history of a weakened immune system from birth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PANDA-VAC and pembrolizumab. The vaccine is administered on Days 1 and 4 of Week 1, Day 1 of Week 2, Day 1 of Week 3, Day 1 of Week 4, Day 1 of Week 11, and Day 1 of Week 21.

21 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

10 years

What Are the Treatments Tested in This Trial?

Interventions

• PANDA-VAC
• Pembrolizumab

Trial Overview The trial tests a personalized vaccine (PANDA-VAC) given alongside Pembrolizumab to see if it's safe for patients with specific types of advanced cancer. It's an early-phase study where all participants receive both treatments and are closely monitored.

How Is the Trial Designed?

Group I: PANDA-VAC combined with pembrolizumab Experimental Treatment 2 Interventions

The final primary therapeutic neoantigen vaccine product will comprise 6 peptides at a dose of 300 μg per peptide and Poly-ICLC at a dose of 500 μg formulated in an aqueous solution containing \<5% DMSO in isotonic dextrose for a total volume of 750 μL. The vaccine will be administered subcutaneously via 3 equal volume (250 μL) injections, one in an arm and one in each leg. The product will be administered on the following schedule: Days 1 and 4 of Week 1, Day 1 of Week 2, Day 1 of Week 3, Day 1 of Week 4, Day 1 of Week 11, and Day 1 of Week 21.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a clinical trial, the combination of the PD-1 inhibitor pembrolizumab with chemotherapy showed a significant improvement in overall survival for patients with newly diagnosed advanced non-squamous non-small cell lung cancer, with a 12-month survival rate of 69.2%.

This survival rate was notably higher compared to the 49.4% survival rate in patients who received chemotherapy alone, indicating that pembrolizumab may enhance the effectiveness of standard chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combo Therapy for Lung Cancer Extends Survival. [2019]

In a study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 1,026 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, pembrolizumab showed an objective response rate of 44.5%, with median progression-free survival of 7.9 months and overall survival of 17.2 months.

Higher PD-L1 expression (≥90%) was linked to better treatment outcomes, while factors like poor performance status and the presence of bone or liver metastases were associated with worse clinical outcomes, indicating the importance of patient selection for pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cortellini, A., Tiseo, M., Banna, GL., et al.[2020]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04266730

Study Details | NCT04266730 | Trial of a Personalized and ... This is a single center, open-label phase I clinical trial designed to determine the safety of personalized and adjusted neoantigen peptide vaccine (PANDA-VAC)

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-04787

Personalized Vaccine (PANDA-VAC) and Pembrolizumab ... Giving PANDA-VAC in combination with pembrolizumab may help strengthen the way the immune system responds to squamous cell non-small cell lung cancer and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430651/

Immune checkpoint inhibitors for PD-1/PD-L1 axis in ... Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with stage iv non-small cell lung cancer. Lung Cancer (2020) 142:63–9.

4. keytruda.com keytruda.com/non-small-cell-lung-cancer/combination-therapy-clinical-trial-results/

Advanced Nonsquamous NSCLC Combination Therapy KEYTRUDA with chemotherapy reduced the risk of cancer spreading, growing, or getting worse by 48% compared to chemotherapy alone. Half of the patients receiving ...

5. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04266730/

Clinical Trial: NCT04266730 Number of adverse events in participants as a measure of safety of personalized and dose adjusted antitumor peptide vaccine (PANDA-VAC) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12190263/

Neoantigen-Based Immunotherapy in Lung Cancer In patients with advanced NSCLC, personalized neoantigen-pulsed DC vaccines have shown promising outcomes with objective response rates (25%), disease control ...

8. unclineberger.org unclineberger.org/news/doctors-eye-personalized-adaptive-cancer-vaccine-panda-vac/

Doctors eye personalized, adaptive cancer vaccine They say an upcoming clinical trial is their shot at curing lung and head and neck squamous cell carcinomas – cancers linked to smoking.