a study to investigate the efficacy and safety of an infusion of iov-4001 in adult participants with unresectable or metastatic melanoma or stage iii or iv non-small-cell lung cancer

Conditions: Unresectable Melanoma; Metastatic Melanoma; Stage III Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Summary: this is a study to investigate the efficacy and safety of an infusion of iov-4001 in adult participants with unresectable or metastatic melanoma or advanced non-small-cell lung cancer (nsclc).

this study is the first-in-human study of iov-4001, a genetically modified autologous tumor- infiltrating lymphocytes (til) product. iov-4001 is expected to have antitumor activity through its capacity to directly target and kill tumor cells in a manner that is similar to non-genome-edited til, but with the potential for enhanced antitumor activity due to disruption of pdcd1, the gene for programmed cell death protein-1 (pd-1).

Eligibility criteria:
inclusion criteria: 1. participants must have a confirmed diagnosis of stage iiic, iiid, or iv unresectable or metastatic melanoma or stage iii or iv nsclc. 2. participants who have received the following previous therapy: 1. cohort 1 (melanoma): participants who have progressed within 12 weeks of last dose of anti-pd-1/pd-l1 blocking antibody and received braf/mek inhibitor in those with braf mutations. 2. cohort 2 (nsclc): participants who should have received no more than 3 prior lines of therapy and: * those without oncogene-driven tumors: have progressed within 12 weeks after last dose of anti-pd-1/pd-l1 blocking antibody * those with oncogene-driven tumors: have progressed during/after ≥1 targeted therapy and either: * platinum doublet chemotherapy * or within 12 weeks after last dose of anti-pd-1/pd-l1 blocking antibody 3. participants who have an eastern cooperative oncology group (ecog) performance status of 0 or 1. 4. participants who is assessed as having at least one resectable lesion. 5. participants who have at least one measurable lesion, following resection of the lesion for iov-4001 generation. 6. participants who have adequate organ function. 7. cardiac function test required. 8. pulmonary function test may be required. 9. participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months. 10. participants who are \>70 years of age may be allowed to enroll after the investigator discusses with the medical monitor. exclusion criteria: 1. participants who have melanoma of uveal/ocular origin. 2. participants who have symptomatic untreated brain metastases. 3. participants who have had a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years. 4. participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose. 5. participants who have any form of primary immunodeficiency. 6. participants who have another primary malignancy within the previous 3 years. 7. participants who have received or will receive a live or attenuated vaccination within 28 days prior to the start of the nma-ld.

Keywords: tumor infiltrating lymphocytes til unresectable melanoma metastatic melanoma stage iii non-small-cell lung cancer stage iv non-small-cell lung cancer pd-1 knockout cell therapy autologous adoptive cell therapy cellular immuno-therapy il-2 non small cell lung cancer nsclc second line lung cancer bronchial neoplasms carcinoma lung disease metastatic lung cancer metastatic non small cell lung cancer lung carcinoma pd-l1 stage iv cancer stage iv lung cancer stage iv nsclc systemic therapy 2nd line therapy second line therapy cpi check point inhibitor metastatic nsclc nsclc recurrent recurrent lung cancer recurrent lung carcinoma autologous adoptive cell transfer melanoma lifileucel stage iii melanoma stage iv melanoma skin cancer skin cancer types malignant melanoma