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

Non-Small Cell Lung Cancer Clinical Trial

Official title: 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

Status Recruiting

Clinical Trial 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.

Clinical Trial Description

Background:

• Cancer-testis (CT) antigens (CTA), particularly those encoded by genes on the X chromosome (CT-X antigens) have emerged as attractive targets for cancer immunotherapy.

• Recent studies suggest that CT-X antigens which are up regulated by epigenetic mechanisms may be preferentially expressed in pluripotent stem/tumor initiating cells that mediate treatment resistance and metastasis of human cancers.

• Whereas pulmonary malignancies express a variety of CT-X antigens, immune responses to these proteins are uncommon in lung cancer patients due to low-level, heterogeneous antigen expression, epigenetic repression of genes regulating antigen processing/presentation, and local as well as systemic immunosuppression in these individuals.

• Conceivably, vaccination of lung cancer patients with tumor cells expressing high levels of CT-X antigens in combination with regimens that inhibit immunosuppressive functions of T regulatory cells and enhance activity of natural killer (NK) cells will induce broad immunity to these antigens.

Primary Objectives:

• 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.

• 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 (Registered Trademark) ISA-51 VG adjuvant in combination with N-803.

Eligibility:

• Participants with pathologically confirmed Stage IB-IIIA (T2a-T4/N0, T1-T3N1, T1-T2/N2) NSCLC per 8th edition TNM Staging System non-small cell lung cancer (NSCLC) who have no clinical evidence of active disease (NED) following standard therapy completed within the past 12 weeks.

• Participants must be 18 years or older with an ECOG performance status of 0-2.

• Participants must have adequate bone marrow, kidney, liver, lung, and cardiac function.

• Participants receiving systemic immunosuppressive medications will be excluded.

• Participants with HIV will be excluded.

Design:

• Following recovery from surgery, and adjuvant therapy if indicated, eligible participants will be vaccinated via deep subcutaneous (SQ) injection with H1299 cell lysate and Montanide (Registered Trademark) ISA-51 VG (Trademark) adjuvant with or without subcutaneous N-803 monthly until six vaccinations have been given.

• Standard of care imaging studies will be performed at baseline, and one month following the 3rd and 6th vaccinations.

• Leukapheresis will be performed at baseline and at treatment evaluation one month following completion of the six vaccinations.

• Systemic toxicities and immunologic responses to therapy will be recorded.

• Pre- and post-vaccination serologic and cell mediated responses to a panel of CT-X antigens will be assessed before and one month following completion of the six vaccinations.

• Individuals deemed to have responded to vaccine treatment and exhibit no evidence of disease recurrence or secondary malignancy will be eligible for 2 additional vaccinations at 3 months after receiving the sixth vaccine and 6 months after receiving the 6th vaccine with N-803.

• Numbers and percentages of immune subsets, soluble factors, and cytokines in peripheral blood will be assessed before and after the six vaccinations.

• Immunologic responses to autologous tumor cells (if available) as well as pooled lung cancer stem cell vs. normal lung-induced pluripotent stem cell (Lu-iPSC) lysates will be evaluated in an exploratory manner.

• Accrual ceiling will be set at 30 participants. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinomas
• Lung Neoplasms
• Non-Small Cell Lung Cancer
• Non-Small Cell Lung Carcinoma

• NCT number: NCT05642195
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Deneise Francis, R.N.
• Phone: (240) 858-3974
• Email: deneise.francis@nih.gov
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 26, 2024
• Completion date: December 30, 2035