A Phase II Multi-Arm (basket) Trial Investigating the Safety and Efficacy of IO102-IO103 in Combination with Pembrolizumab, as First-line Treatment for Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC), Squamous Cell Carcinoma of Head and Neck (SCCHN), or Metastatic Urothelial Bladder Cancer (mUBC)

You may be able to join if

• Patients with histologically or cytologically confirmed: Metastatic NSCLC (adenocarcinoma) (Cohort A), who have not received prior systemic treatment for their metastatic disease and who have: •No known sensitizing genetic aberrations where there are approved therapies (such as ALK, ROS1, EGFR, BRAF V600E, MET skipping mutations, and RET mutations or rearrangements) or SCCHN (Cohort B) with no prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease) and who have: •SCCHN considered incurable by local therapies. Tumors of nasopharyngeal origin (any histology) are excluded •Documented results of p16/HPV status for oropharyngeal cancer (per institution standard) or Metastatic UBC (Cohort C) with no prior therapy and not eligible for any platinum-containing chemotherapy: •Urothelial cancer of the renal pelvis, ureter, bladder or urethra (transitional cell and mixed transitional/non transitional cell histologies permitted but transitional cell histology must be the dominant histology) For all cohorts, any solitary metastases must be biopsied to confirm diagnosis of metastases from primary indication.
• Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of trial treatment. Adequate organ function as defined by: •Haematology: Absolute neutrophil count ≥1500/µL or ≥1.5 × 109/L, Platelets ≥100,000/µL or ≥100 × 109/L, Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L. Criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin (≥ approximately 3 months). •Renal: Creatinine ≤1.5 × upper limit of normal (ULN), or Measured or calculated creatinine clearance (CrCl) ≥50 mL/min for patients with creatinine levels >1.5 × institutional ULN; GFR can also be used in place of creatinine or CrCl •Hepatic: Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 × ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for patients with liver metastases), Alkaline phosphatase ≤2.5 × ULN •Endocrine: No uncontrolled endocrinopathies •Coagulation: International normalised ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment initiation. Note: Patients should remain on anti-viral therapy throughout trial treatment and follow local guidelines for HBV anti-viral therapy after completion of trial treatment. Hepatitis B screening tests are not required unless: a. Known history of HBV infection b. As mandated by local health authority
• Patients with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Note: Patients must have completed curative anti-viral therapy at least 4 weeks before treatment initiation. Hepatitis C screening tests are not required unless: a. Known history of HCV infection b. As mandated by local health authority
• PD-L1 TPS or PD-L1 CPS (as confirmed prior to enrolment using the PD-L1 IHC DAKO 22C3 PharmDx assay, using local or central services): •Cohort A (NSCLC adenocarcinoma): PD-L1 TPS ≥50% •Cohort B (SCCHN): PD-L1 CPS ≥20; HPV +/- •Cohort C (mUBC): PD-L1 CPS ≥10
• A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies: •Not a woman of childbearing potential (WOCBP) •A WOCBP who agrees to follow contraceptive guidance starting with the screening visit and through 120 days after last dose of pembrolizumab or 180 days after last dose of chemotherapy. Note: A WOCBP, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Tubal ligation is not a method of permanent sterilisation. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.