- Non-small cell lung cancer (NSCLC) Cohort: Histologically or cytologically confirmed
diagnosis of NSCLC that is locally advanced or metastatic; No activating EGFR
mutations, ALK or ROS1 translocations/rearrangements where testing is standard of
care; received at least 1 prior platinum‑based chemotherapy regimen for locally
advanced or metastatic NSCLC; No more than 2 prior lines of systemic therapy for
locally advanced or metastatic disease (If disease progression occurred during or
within 6 months after neoadjuvant/adjuvant chemotherapy or radiotherapy‑chemotherapy,
the regimen is counted as 1 prior treatment regimen towards the allowed limit of prior
treatment regimens); Checkpoint inhibitor naïve.
- Urothelial Cancer (UC) Cohort: Histologically or cytologically confirmed diagnosis of
transitional cell carcinoma (TCC) of the urothelium (if mixed, more than 50% TCC
component) including bladder, urethra, ureters, or renal pelvis that is locally
advanced or metastatic; No prior systemic treatment for locally advanced or metastatic
disease; Prior neoadjuvant or adjuvant therapy is permitted if disease progression
occurred >12 months after the completion of therapy; Checkpoint inhibitor naïve;
Ineligible for receiving cisplatin‑containing front‑line chemotherapy based at least
one of the following criteria: ECOG performance status (PS) 2; Renal dysfunction
(defined as creatinine‑clearance
hearing loss (hearing loss measured by audiometry of 25 decibels at two contiguous
frequencies).
- At least 1 measurable lesion by RECIST v1.1 not previously irradiated.
- Availability of an archival FFPE tumor tissue block from primary diagnosis specimen or
metastatic specimen or 15 unstained slides (10 minimum). If an archived sample is not
available, a fresh tumor biopsy must be performed.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. For UC
patients, ECOG performance 2 is permitted (cisplatin ineligibility criterion)
- Prior immunotherapy with an anti?PD?1, anti?PD?L1, anti?PD?L2, anti?CD137, anti?OX?40,
anti?GITR, anti?LAG?3, anti?TIM?3 or anti?CTLA?4 antibody (including ipilimumab).
- Newly diagnosed brain metastases or known symptomatic brain metastases requiring
steroids.
- Radiologically documented evidence of major blood vessel invasion or encasement by
cancer or intratumor cavitation, regardless of tumor histology.
- Active autoimmune disease (that might deteriorate when receiving an immunostimulatory
agent).
- Current use of immunosuppressive medication (except for those listed in protocol).
- Known prior severe hypersensitivity to the investigational products /monoclonal
antibodies.
- Known history of immune?mediated colitis, inflammatory bowel disease, immune?mediated
pneumonitis, pulmonary fibrosis.
- NCI CTCAE Grade 3 hemorrhage within 28 days prior to study enrollment.