IO102-IO103 in Combination With Pembrolizumab as First-line Treatment for Patients With Metastatic NSCLC, SCCHN, or mUBC

Inclusion Criteria

• Patients with histologically or cytologically confirmed:

Metastatic NSCLC (Arm A), who have not received prior systemic treatment for their metastatic disease and who have:

• no known sensitizing EGFR or ALK mutations.

or

Metastatic SCCHN (Arm B) with no prior therapy and who have:

• Histologically- or cytologically-confirmed recurrent or metastatic SCCHN considered incurable by local therapies. Tumors of nasopharyngeal origin (any histology) are excluded
• Documented results of HPV status for oropharyngeal cancer.

or

Metastatic UBC (Arm C) with no prior therapy and not eligible for any cisplatin therapy:

• Advanced/unresectable (inoperable) or metastatic 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)

All solitary metastases must be biopsied to confirm diagnosis of metastases from primary indication

• PD-L1 tumor expression or PD-L1 CPS (as confirmed prior to enrolment using the DAKO 22C3 assay, using local/central services):
• Arm A (NSCLC): PD-L1 TPS ≥ 50%
• Arm B (SCCHN): PD-L1 CPS ≥ 20; HPV +/-
• Arm C (mUBC): PD-L1 CPS ≥ 10
• A male participant able to father a child must agree to use contraception starting with the screening visit and through 120 days after last dose of pembrolizumab or 180 days after last dose of treatment with IO102-IO103.
• 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.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial in accordance with ICH-GCP and local legislation prior to admission to the trial.
• At least 18 years of age on day of signing informed consent
• Have measurable disease per RECIST 1.1 as assessed by local site investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have provided a blood sample and archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides.
• Have an ECOG performance status of 0 to 1.
• If participant received major surgery, they must have recovered adequately from the adverse events and/or complications from the intervention prior to starting trial treatment.
• Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of trial treatment.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 x 109/L Platelets ≥ 100,000/µL or ≥ 100 x 109/L Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L • Renal: Creatinine ≤ 1.5 x ULN, or Measured or calculated creatinine clearance (CrCl) ≥ 60 mL/min for patients with creatinine levels > 1.5 x institutional ULN; GFR can also be used in place of creatinine or CrCl • Hepatic: Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels ≤3 x ULN AST and ALT ≤ 2.5 x ULN (≤ 5xULN for patients with liver metastases) Alkaline Phosphatase ≤ 2.5 x ULN

• Endocrine: Thyroid stimulating hormone (TSH) within normal limits, or Total T3 is within normal limits, or Free T3 and free T4 are within the normal limits
• Coagulation:

International normalised ratio, PT or aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or aPTT is with