Hiram

Researchers are evaluating the drug disitamab vedotin, alone or combined with pembrolizumab, to treat urothelial cancer that expresses HER2. This cancer is locally advanced, cannot be removed by surgery, or has spread to other parts of the body. The study aims to see how well the drug works and how safe it is for participants by monitoring side effects and treatment responses. Participants will receive disitamab vedotin through an intravenous (IV) infusion every two weeks. Pembrolizumab, when given, is administered by IV on the first day of each six-week cycle. The study includes several groups, called cohorts, each with different treatment histories and eligibility criteria. Treatment and evaluation may continue for about two years. During the study, participants will have regular tests including scans to measure tumor response, lab tests, heart function checks, and monitoring for adverse events. Researchers will also track drug levels in the blood and any changes in heart function. The study will assess confirmed tumor responses and safety outcomes over approximately two years, with close monitoring to understand how participants respond to the treatments and any side effects experienced.

Researchers are studying the effects of Adagrasib alone and combined with pembrolizumab in adults with advanced or metastatic non-small cell lung cancer (NSCLC) who have the KRAS G12C mutation. The Phase 2 part evaluates these treatments in patients who are candidates for first-line therapy, with different groups based on their PD-L1 tumor proportion scores (TPS). The Phase 3 part compares the combination of Adagrasib and pembrolizumab against pembrolizumab alone in patients with NSCLC having PD-L1 TPS of 50% or higher. In Phase 2, there are three patient groups: two with PD-L1 TPS less than 1% randomized to receive either Adagrasib monotherapy or Adagrasib plus pembrolizumab, and one group with PD-L1 TPS of 1% or higher treated with the combination. Adagrasib is given orally at doses of 400 mg twice daily or 600 mg twice daily depending on the group, while pembrolizumab is administered intravenously at 200 mg every three weeks. Phase 3 patients are randomized to receive either Adagrasib 400 mg twice daily plus pembrolizumab 200 mg every three weeks or pembrolizumab alone. Participants will undergo various assessments including brain imaging, tumor measurements, and evaluations of safety and treatment effects over 22 months in Phase 2 and 36 months in Phase 3. Researchers will monitor efficacy, safety, and drug levels, as well as patient-reported outcomes and genetic biomarkers. The study includes patients with untreated or previously treated brain metastases under specific conditions and excludes those with prior systemic treatments for advanced NSCLC or certain brain lesion characteristics.