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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

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) administered concurrently with pembrolizumab in subjects with advanced squamous non-small cell lung cancer (NSCLC) or squamous cell carcinoma of head and neck (SCCHN).

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.

What data supports the effectiveness of the drug PANDA-VAC + Pembrolizumab for lung cancer?

Research shows that pembrolizumab, a part of the treatment, has been effective in improving survival rates for patients with advanced non-small cell lung cancer when used alone or in combination with chemotherapy. ^{1 2 3 4 5}

Is the combination of PANDA-VAC and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been studied in many patients with lung cancer and is generally considered safe, but it can cause side effects like lung issues, hormone problems, liver issues, severe diarrhea, infusion reactions, and skin problems. Most side effects happen within 150 days of starting treatment. ^{1 2 6 7 8}

What makes the PANDA-VAC + Pembrolizumab treatment unique for lung cancer?

The PANDA-VAC + Pembrolizumab treatment is unique because it combines a novel vaccine (PANDA-VAC) with pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the immune response against lung cancer, potentially offering a new approach compared to standard treatments. ^{1 2 3 8 9}

Research Team

Jared Weiss, MD

Principal Investigator

UNC Chapel Hill

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Combo Therapy for Lung Cancer Extends Survival. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. [2020]

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Real-world outcomes of pembrolizumab monotherapy in non-small cell lung cancer in Japan: A post-marketing surveillance. [2022]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]