Gainesville

This research aims to evaluate the safety and effectiveness of the combination of avutometinib and defactinib compared to standard treatments chosen by investigators in women with recurrent low-grade serous ovarian cancer (LGSOC) who have experienced disease progression after prior platinum-based therapy. Both avutometinib and defactinib are investigational kinase inhibitors designed to block cancer cell growth. The study will also assess overall survival, other measures of treatment effectiveness, safety, and quality of life impacts. Participants will be randomly assigned to receive either the combination of oral avutometinib and defactinib or one of four standard treatments recommended for recurrent LGSOC: pegylated liposomal doxorubicin and paclitaxel (both given intravenously), or the oral drugs letrozole or anastrozole. Patients treated with standard therapies who experience disease progression may be eligible to switch to the investigational combination. The study is open-label and conducted internationally by specialists in gynecological cancer. Throughout the study, participants will have regular follow-up visits including scans and tests to measure disease progression, with a primary focus on progression-free survival up to 24 months. Researchers will monitor safety, side effects, and overall survival while collecting information on quality of life and symptoms. The study involves ongoing assessments of treatment effects and participant health until the study concludes or disease progression occurs.

Researchers are evaluating the effectiveness and safety of sonrotoclax combined with zanubrutinib compared to zanubrutinib with a placebo in adults who have relapsed or refractory mantle cell lymphoma (MCL), a type of B cell lymphoma. This phase 3 study aims to understand how well these treatments work in patients who have already undergone previous therapies and have measurable disease. The study is sponsored by BeOne Medicines, previously known as BeiGene. Participants will receive either sonrotoclax plus zanubrutinib or zanubrutinib plus placebo, with all drugs administered orally. The treatments will be given in a double-blind, randomized manner across multiple centers. The study focuses on comparing the progression-free survival of participants over approximately 41 months, as assessed by an independent review committee. During the study, participants will be closely monitored for disease progression and safety outcomes. Assessments will include confirmation of diagnosis through tumor tissue analysis, evaluation of measurable disease lesions, and ongoing monitoring of organ function and performance status. The study duration and follow-up will allow researchers to assess long-term treatment effects and safety in the target adult population with relapsed or refractory MCL.

Researchers are evaluating the effectiveness of a combination treatment involving adagrasib, pembrolizumab, and chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation. This Phase 2 trial focuses on patients with PD-L1 tumor proportion score (TPS) of 1% or higher, but less than 50%, who have not received prior systemic therapy for advanced disease. The study aims to assess how well this combination works as a first treatment option for this patient group. Participants receive adagrasib as oral tablets twice daily at a dose of 400 mg. Pembrolizumab and chemotherapy drugs (pemetrexed and either cisplatin or carboplatin) are given by intravenous infusion once every three weeks. The study includes several groups based on prior treatments and PD-L1 levels, with some participants having previously completed induction chemotherapy. Treatments are administered according to these schedules and patient eligibility. During the study, researchers monitor participants for tumor response and progression-free survival over 30 months. They use standard criteria to measure tumor size changes and disease progression. Assessments include clinical evaluations and imaging to track response to treatment. Safety and tolerability are also monitored throughout the study period to understand the effects of the combination therapy on patients.

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.