Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With or Without the IL-15 Super-Agonist N-803 as Adjuvant Therapy for PD-L1 Negative Non-Small Cell Lung Cancer

Plain English Summary

Evaluation of a Cancer Lysate Vaccine and Montanide (Registered Trademark) ISA-51 VG With or Without the IL-15 Super-Agonist N-803 as Adjuvant Therapy for PD-L1 Negative Non-Small Cell Lung Cancer is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma, Carcinoma, Non-Small-Cell Lung, Carcinomas. This trial tests a new cancer vaccine made from lung cancer cells, combined with an immune-boosting drug, to help prevent non-small cell lung cancer from returning after surgery. It is for adults who have had surgery for non-small cell lung cancer and have no signs of the cancer returning, specifically those whose cancer cells have low PD-L1 expression. Participation involves receiving a series of under-the-skin injections of the vaccine and drug over several months, followed by regular check-ups and scans for up to 5 years. Alternative treatments after surgery may include chemotherapy, radiation, or other immunotherapies, depending on the individual's cancer and overall health. The trial aims to enroll 30 participants.

Official Summary

Background: Surgery is the primary treatment for non-small cell lung cancer (NSCLC) that is diagnosed in its earlier stages. But the tumors often return. Radiation and chemotherapy can improve survival in some people who have had surgery for NSCLC, but these treatments also cause serious side effects. A new approach, called immunotherapy, may be a better way to stop NSCLC tumors from coming back. Objective: To test a new treatment (H1299 lung cancer cell vaccine combined with the drug N-803) in people who received surgery for NSCLC. Eligibility: Adults aged 18 years or older with no sign of disease after surgery for NSCLC. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and lung function. They will have imaging scans. Study treatment will be given in 28-day cycles. Participants will visit the clinic on the first day of each cycle. They will receive 2 treatments at each visit: The study vaccine is given as 2-4 small shots under the skin of the thigh or arm. N-803 is given as a shot under the skin of the abdomen. Treatment will continue for 6 cycles. Blood tests and imaging scans will be repeated throughout the study. Participants will have a blood test 1 month after receiving the 6th vaccine. Some participants may then resume taking N-803; they may also receive 2 more vaccinations at 3 and 6 months after their previous treatment. Follow-up visits will continue for up to 5 years.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a specific type of non-small cell lung cancer (Stage IB-IIIA) that has been surgically removed. Patients must have no current signs of cancer and have low PD-L1 expression on their cancer cells. Individuals must be within 12 weeks of completing prior cancer treatment and have good general health, including adequate blood counts, kidney, and liver function. People with active infections, uncontrolled high blood pressure, certain heart or lung conditions, or those currently receiving other cancer treatments are not eligible. This trial is studying Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma, Carcinoma, Non-Small-Cell Lung, Carcinomas, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will assess how well the vaccine and drug combination stimulates the body's immune system to fight any remaining cancer cells and determine if this new treatment is safe f The specific primary outcome measures are: Phase II Component: To assess the frequency of immunologic responses to purified CT-X and autosomal CT antigens in NSCLC participants following vaccinations with H1299 cancer cell lysate and Montanide ISA-51 VG adjuvant in combination with N-803 (1 month following first 6 vaccinations, and every 6 months during retreatment); Phase I Component: To determine the safety of H1299 lung cancer cell lysate vaccines administered with Montanide (Registered Trademark) ISA-51 VG adjuvant and N-803 (before each cycle, every 2 weeks between vaccines 1 & 2 (AE only), at each treatment evaluation, and at the safety visit). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to address the significant challenge of lung cancer recurrence after surgery by exploring a novel vaccine-based immunotherapy that could offer a more effective way to keep the cancer a Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma, Carcinoma, Non-Small-Cell Lung, Carcinomas, where improved treatment options are needed.

Investor Insight

This trial, though currently suspended, represents an investment in novel immunotherapy approaches for lung cancer, a large market with a significant unmet need for effective adjuvant therapies, sugge Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific type of lung cancer and overall health. Understand that participation involves regular clinic visits for injections and monitoring, including physical exams, blood tests, and imaging scans. Be prepared for potential side effects and the commitment to follow-up visits for up to 5 years after treatment. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 30 participants

Interventions

• BIOLOGICAL: Montanide (Registered Trademark) ISA-51 VG Adjuvant — H1299 cell lysate with Montanide (Registered Trademark) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mcg lysate protein in 2-2.5 mL Montanide (Registered) ISA-51 VG adjuvant; lysate concentration will be 8-10 mcg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED.
• BIOLOGICAL: H1299 Cell Lysates — H1299 cell lysate with Montanide (Registered) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mcg lysate protein in 2-2.5 mL Montanide (Registered Trademark) ISA-51 VG adjuvant; lysate concentration will be 8-10 mcg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED.
• DRUG: N-803 — N-803 via subcutaneous injection in the abdomen at dose of 15 ug/kg every 4 weeks, on Day 1 of each cycle. N-803 dosing will be calculated using a weight obtained within 5 days prior to the first dose. Dose re-calculated at the beginning of each subsequent cycle in the event of a 10% or greater weight change.
• DEVICE: Ventana PD-L1 (SP263 or SP142) assay — FDA-approved assays used off-label for study as treatment determining in-vitro diagnostic devices to assess subject PD-L1 quantitation. Testing will be performed on provided archival samples or on fresh sample that is collected at screening for confirmation of diagnosis; no additional sample collection for purposes of PD-L1 testing.

Primary Outcomes

• Phase II Component: To assess the frequency of immunologic responses to purified CT-X and autosomal CT antigens in NSCLC participants following vaccinations with H1299 cancer cell lysate and Montanide ISA-51 VG adjuvant in combination with N-803 (1 month following first 6 vaccinations, and every 6 months during retreatment)
• Phase I Component: To determine the safety of H1299 lung cancer cell lysate vaccines administered with Montanide (Registered Trademark) ISA-51 VG adjuvant and N-803 (before each cycle, every 2 weeks between vaccines 1 & 2 (AE only), at each treatment evaluation, and at the safety visit)

Secondary Outcomes

• To determine disease-free survival (DFS) in lung cancer participants receiving adjuvant H1299 lung cancer cell lysate vaccines administered with Montanide (Registered Trademark) ISA-51 VG and N-803 (every 12 weeks while on treatment, during follow up for every 3 months for 3 years then every 6 months for 2 years or disease progression, final DFS evaluation visit)

Full Eligibility Criteria

* INCLUSION CRITERIA:
* Participant with histologically or cytologically proven Stage IB-IIIA (T2a-T4/N0, T1- T3N1, T1-T2/N2) NSCLC per 8th edition TNM Staging System with no clinical evidence of active disease (NED) or minimal residual disease (MRD) not readily accessible by non-invasive biopsy or resection/radiation following standard therapy. Initial diagnosis must be confirmed by the NIH Laboratory of Pathology.
* History of PD-L1 expression in cancer cells \< 1% as determined by IHC analysis.
* Participant must be enrolled within 12 weeks following completion of prior SOC therapy.
* Participant must have an ECOG performance status of 0-2.
* Participant must be \>=18 years of age.
* Participant must be willing to co-enroll on protocol 06C0014 (Prospective Analysis of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) allowing for the collection of blood for correlative experiments pertaining to this protocol and related translational research efforts in the Thoracic Surgery Branch.
* Participant must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters (all eligibility assessment/enrollment bloodwork must be done at NIH no more than 2 weeks prior to enrollment):
* Absolute neutrophil count greater than 1500/mm3
* Absolute lymphocyte count greater than 800/mm3
* Platelet count greater than 75,000/mm3
* Hemoglobin greater than 8 g/dL (participant may receive transfusions to meet this parameter)
* INR\< 1.5xULN
* Total bilirubin \< 1.5 x upper limits of normal (except those with Gilberts disease)
* Serum creatinine less than or equal to 1.6 mg/mL or the eGFR must be greater than 60 mL/min/1.73m2
* Seronegative for HIV antibody by bloodwork performed at NIH no more than 4 weeks prior to enrollment.
* Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RTPCR and be HCV RNA negative by bloodwork performed at NIH no more than 4 weeks

prior to enrollment.

* Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while receiving investigational treatment and for 120 days after the last dose of vaccine or N-803.
* Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) within 28 days prior initiation of study therapy, for the duration of study participation and up to 120 days after the last

dose of the drug.

-Participant must be able to understand and willing to sign an informed consent.

EXCLUSION CRITERIA:

* Participants receiving other investigational agents.
* Participants on any active treatment for their cancer upon study entry.
* Participant who is initially rendered NED or have MRD following standard therapy but exhibit disease progression prior to initiation of vaccination.
* Participant requiring chronic systemic treatment with steroids above physiologic doses.
* Participant receiving warfarin anticoagulation, who cannot be transitioned to other agents such as enoxaparin or dabigatran, and for whom anticoagulants cannot be held for up to 24 hours.
* Participant with uncontrolled hypertension (\> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated CHF (\> NYHA Class II), or myocardial infarction within 6 months prior to initiation of study therapy.
* Participant with any of the following pulmonary function abnormalities: FEV, \< 35% predicted; DLCO \< 35% predicted (post-bronchodilator); oxygen saturation less than 92% on room air based on assessment at NIH or outside medical facility no more than 4 weeks prior to protocol enrollment.
* Active COVID infection
* Participant pregnancy
* Uncontrolled intercurrent illness occurring within 3 months prior to initiation of study therapy /social situations (as assessed by social services) that would limit compliance with study requirements.

Trial Locations

• National Institutes of Health Clinical Center, Bethesda, Maryland, United States

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Carcinoma
• Thoracic Malignancies
• Cancer Immunotherapy
• Adjuvant Therapy
• Cancer Vaccines
• Tumor Recurrence
• Oncology
• Pulmonary Oncology

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