AI-Designed vaccine takes on lung cancer in new trial

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: \- Subjects are eligible if all of the following are met: Age ≥18 years at the time of informed consent. Diagnosis / Histology Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is: Non-squamous (e.g. adenocarcinoma, large-cell, NSCLC-NOS adjudicated non-squamous), or Squamous (if/when that stratum is open). Diagnosis must be locally documented and source-verifiable. Stage / Disease Status Stage IIIB / IIIC / IV or recurrent/metastatic NSCLC not amenable to curative surgery or radiotherapy, per AJCC 8th edition staging. Disease is considered first-line metastatic/systemic setting: No prior systemic therapy for advanced/metastatic disease in this line. Prior adjuvant/neoadjuvant therapy or consolidation chemo-RT is allowed if completed and the subject relapsed outside the protocol-defined disease-free interval (e.g. relapse ≥6-12 months after completion, per final protocol text). Measurable Disease At least one measurable lesion per RECIST v1.1 at baseline imaging. Baseline imaging must be within 28 days prior to Day 1 (CT chest/abdomen/pelvis ± contrast, plus brain MRI if clinically indicated). ECOG Performance Status ECOG 0 or 1 at screening. Subject must be ambulatory and clinically stable enough to receive combination therapy (pembrolizumab + chemo ± Microlyvaq™). Adequate Organ and Marrow Function (Representative thresholds - to be finalized numerically in the protocol SOP, but typically:) Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L. Platelets ≥100 × 10⁹/L. Hemoglobin ≥9.0 g/dL (transfusion allowed per institutional standard prior to enrollment). AST and ALT ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN if liver metastases are present. Total bilirubin ≤1.5 × ULN (≤3 × ULN if known Gilbert's syndrome). Creatinine clearance / eGFR ≥45 mL/min/1.73 m² (sufficient for pemetrexed/platinum; final numeric cutoff may align to pemetrexed label). Coagulation: INR and aPTT compatible with safe biopsy (if biopsy expected) per site policy. Oxygenation: No resting hypoxemia prohibitive for safe treatment in investigator judgment. Tumor Tissue Availability Adequate tumor material must be available for: PD-L1 assessment, DNA/RNA extraction (whole exome sequencing / RNA-seq or targeted panel sufficient for epitope discovery), High-resolution HLA typing support, Optional spatial profiling. Acceptable sources: Recent core needle biopsy or surgical specimen (preferred), OR Archival FFPE block or ≥15 unstained slides with documented tumor cellularity. Tumor cellularity must meet the minimum input requirement for sequencing and PD-L1 scoring (macrodissection allowed). Biospecimen / Translational Willingness Willing and able to provide required blood samples at protocol-defined timepoints: PBMC (for ELISpot, ICS, TCR sequencing), Plasma/serum (for ctDNA, exosomal miRNA, cytokines), HLA typing. Willing to allow shipment of these biospecimens under chain-of-custody to central labs. Willing to undergo optional on-treatment biopsy (e.g. around Cycle 3 / \~Week 6-9) if, in the investigator's judgment, it is clinically safe and technically feasible. If unsafe, liquid biopsy alone is acceptable. Contraception / Reproductive Status Females of childbearing potential: negative pregnancy test at screening and prior to first dose. Females of childbearing potential and males with partners of childbearing potential must agree to use highly effective contraception during study treatment and for the protocol-defined post-treatment window: Typically ≥120 days after last pembrolizumab dose and ≥90 days after last Microlyvaq™ dose, whichever is longer (final timing per protocol). No intention to conceive or donate gametes during this protection window. Informed Consent Capable of understanding and signing informed consent(s), including: Main study consent (chemo + pembrolizumab + Microlyvaq™), Genomic profiling / HLA typing consent, Optional on-treatment biopsy / leukapheresis consent (if applicable at site), Data/privacy language (GDPR-compliant). Willing to comply with study visits, dosing schedule, safety monitoring, PRO questionnaires (if enrolled in PRO subset), and survival follow-up. Exclusion Criteria: Subjects must not meet any of the following: Prior Systemic Therapy in Metastatic Setting Any prior systemic therapy for metastatic / unresectable NSCLC in the current line. Exception: prior adjuvant/neoadjuvant chemo, IO, or chemoradiation allowed if relapse occurred outside the protocol's defined exclusion interval (e.g. relapse ≥6-12 months after completion); exact interval to be specified. Known Oncogene-Addicted Disease Requiring Targeted SOC Subjects whose tumors harbor actionable drivers for which an approved targeted therapy is standard first-line care (e.g. EGFR activating mutation, ALK rearrangement, ROS1 rearrangement, certain ERBB2/HER2 drivers, MET exon 14 skipping, RET fusion, NTRK fusion, KRAS G12C where local standard is targeted frontline) may be excluded or enrolled only in specific sub-cohorts if allowed by the statistical design. Rationale: It may be unethical to withhold proven first-line targeted agents. The final protocol will define whether these genotypes are (a) excluded, (b) stratified, or (c) routed to a molecularly restricted exploratory cohort. Uncontrolled CNS Disease Active, symptomatic brain metastases or leptomeningeal disease requiring immediate local intervention. Allowed: Previously treated/stable brain metastases are permitted if: Clinically stable, Off high-dose steroids (e.g. \>10 mg prednisone equivalent daily) for ≥14 days before Day 1, No new/worsening neurologic symptoms for ≥2 weeks. Excluded: Ongoing steroid dependency above immunosuppressive thresholds, uncontrolled seizures, mass effect with high intracranial pressure, or unstable neuro deficits judged unsafe. Autoimmune / Immune-Mediated Conditions of Concern Active, uncontrolled autoimmune disease that has required systemic immunosuppression \>10 mg/day prednisone-equivalent (or biologic immunosuppressive agent) within 14 days prior to Day 1. History of severe (life-threatening) immune-related adverse event (irAE) to prior PD-1/PD-L1/CTLA-4 (e.g. Grade 4 pneumonitis, myocarditis, neurologic irAE that did not fully resolve), unless cleared by Medical Monitor. Autoimmune disorders that are mild, stable, and not expected to flare under PD-1 blockade (e.g. controlled hypothyroidism on replacement; vitiligo; stable type 1 diabetes on insulin) may be allowed. Significant Active Infection Any uncontrolled active infection requiring IV antibiotics or hospitalization at screening. Uncontrolled HBV, HCV, or HIV viremia above protocol thresholds: HBV: high viral load without appropriate antiviral management. HCV: untreated, high-level viremia with ongoing hepatic decompensation. HIV: uncontrolled (e.g. not on stable antiretroviral therapy, CD4 below a prespecified safe cutoff); final numeric cutoffs defined in protocol. Active tuberculosis or other serious opportunistic infection. Clinically Significant Pulmonary Compromise Baseline pneumonitis requiring steroids. Prior ≥Grade 3 immune-mediated pneumonitis from checkpoint inhibitor therapy that did not resolve to ≤Grade 1. Severe, uncontrolled interstitial lung disease that would make pembrolizumab plus investigational immunostimulation unsafe. Other Serious Uncontrolled Comorbidities Uncontrolled congestive heart failure, unstable angina, recent myocardial infarction or stroke (typically \<6 months). Clinically significant uncontrolled arrhythmia. Severe uncontrolled hypertension. Any condition that, in the investigator's judgment, would make study therapy unacceptably high risk (e.g. ECOG drift, frailty, severe malnutrition). Bleeding Risk / Biopsy Unsuitability (When Biopsy is Expected) Active, clinically significant bleeding or coagulopathy that cannot be corrected. Platelet count or anticoagulation status that, in investigator judgment, makes mandatory biopsy unsafe. NOTE: If a site/arm requires an on-treatment biopsy for core analysis and it is deemed unsafe, subject may still be eligible if protocol allows liquid-biopsy-only participation in that stratum. (This must be explicitly permitted to avoid excluding medically fragile patients.) Known Hypersensitivity Known severe hypersensitivity (e.g. anaphylaxis) to pembrolizumab, to the planned chemotherapy backbone (e.g. pemetrexed, carboplatin) despite standard premedication strategies, or to critical Microlyvaq™ excipients / adjuvant components. In pemetrexed-containing regimens: inability/unwillingness to receive mandatory folate and vitamin B12 supplementation and steroid premedication. In carboplatin regimens: uncontrolled prior carboplatin hypersensitivity not manageable by desensitization. Pregnancy / Breastfeeding Pregnant or breastfeeding at screening. Intention to become pregnant (or impregnate a partner) during study therapy or within the required contraception window after last dose. Concurrent Participation in Confounding Interventional Trials Enrollment in another interventional clinical study that could confound efficacy/safety readouts or interfere with immune profiling. Exceptions: Non-interventional / observational registries, Certain supportive care trials with Medical Monitor approval, Protocol-approved combination substudies (if integrated under the Microlyvaq™ umbrella and statistically planned). Any Condition That Interferes With Protocol Compliance Inability or unwillingness to comply with: Scheduled visits, Biospecimen collections (for HLA typing, PBMC isolation, ctDNA, etc.), Imaging schedule (q6 weeks through Week 24, then q9-12 weeks), Safety follow-up and PRO questionnaires (if PRO subset), Survival follow-up calls \~q12 weeks post-treatment. Cognitive, psychiatric, or social situations that in the investigator's judgment would preclude safe, reliable participation and follow-up. Notes / Operational Clarifiers HLA typing and sequencing feasibility: The subject must have enough viable tumor + PBMC DNA/RNA to allow: WES / RNA-seq or equivalent targeted sequencing for neoantigen discovery, High-resolution HLA-A/B/C typing. If a subject cannot generate a viable personalized epitope set (e.g. insufficient material for immunogen design), that subject may be ineligible for Microlyvaq™ dosing but could be eligible for safety follow-up / SOC reference cohorts, depending on how the arm is structured. Brain metastases: Stable, treated, asymptomatic brain mets are allowed. This matters in first-line metastatic NSCLC, because excluding all brain mets would make the trial clinically irrelevant. The key exclusion is uncontrolled CNS disease requiring urgent steroids/radiation/surgery. Actionable oncogene drivers: Final protocol must say explicitly whether EGFR/ALK/ROS1/etc. are: excluded entirely, allowed but stratified, or diverted to exploratory "post-standard-targeted-therapy" cohorts. This is both ethical and regulatory: you don't want to randomize someone away from globally recognized, mutation-directed SOC. Autoimmune disease: The bar is not "no autoimmune history ever." It's "no uncontrolled, high-risk autoimmune activity that would likely flare catastrophically when we give a personalized Th1-skewing vaccine + PD-1 blockade." Contraception window: Needs to line up with pembrolizumab label and with any reproductive toxicity data from Microlyvaq™ (e.g. ≥120 days / ≥90 days windows). Keep that harmonized across patient materials, pharmacy manual, and consent. This criteria block is inspection-facing: it protects safety, preserves interpretability of immune endpoints, ensures we can actually manufacture/deliver a personalized Microlyvaq™ lot, and keeps the population consistent with first-line pembrolizumab+chemo standards in advanced NSCLC.