Phase 1/2 Study of Combination Immunotherapy and Messenger Ribonucleic Acid (mRNA) Vaccine in Subjects With NSCLC

Adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 20.0 and classified by MedDRA system organ class (SOC) and preferred term. The severity was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. AEs were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. TEAEs are AEs that occurred or worsened in severity after administration of the first dose of study treatment.

For each arm, the first 6 subjects were evaluated for dose limiting toxicities (DLTs).

Deaths within the AE Reporting Period included all deaths that occurred during the study treatment period, or up to 90 days after the administration of the last dose of study drug or initiation of a new treatment.

Progression Free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or to the date of death, if disease progression did not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions.

Progression-free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression did not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions.

Progression-free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression according to immune related Response Evaluation Criteria in Solid Tumors (irRECIST) or to the date of death, if disease progression did not occur. Per irRECIST, progressive disease (irPD) is defined as a ≥ 20% increase from nadir in the total measurable tumor burden (TMTB).

Progression-free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression did not occur. Per irRECIST, progressive disease (irPD) is defined as a ≥ 20% increase from nadir in the total measurable tumor burden (TMTB).

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions; stable disease (SD): small changes that do not meet above criteria.

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions or presence of new lesions; stable disease (SD): small changes that do not meet above criteria. An Objective Response is defined as a CR or PR over a period of at least 4 weeks.

Duration of Response (DoR) was defined as the interval between the date of earliest determination of CR or PR to the date of earliest determination of progressive disease (PD), clinical progression or death, whatever occurred first.

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per irRECIST, responses are categorized as follows: Complete Response (irCR): Complete disappearance of all target lesions; Partial Response (irPR): ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); Progressive Disease (irPD): ≥ 20% increase from nadir in TMTB; Stable Disease (irSD): not meeting above criteria.

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per irRECIST, responses are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria.

An Objective Response is defined as an irCR or irPR over a period of at least 4 weeks.

Duration of Response (DoR) was defined as the interval between the date of earliest determination of irCR or irPR to the date of earliest determination of progressive disease (irPD), clinical progression or death, whatever occurred first.

After completion of treatment, all subjects were followed for survival every 6 months following initiation of study treatment until October 29, 2021 when all post-study follow-up was completed. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive.