Pergamino

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the effectiveness of Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.

Researchers are evaluating whether tucatinib combined with trastuzumab and mFOLFOX6 works better than the standard treatments for people with HER2 positive metastatic colorectal cancer, which is cancer that has spread or cannot be removed by surgery. This phase 3 study also aims to identify the side effects that may occur with this drug combination. Participants must have HER2 positive disease confirmed by testing and measurable cancer according to specific criteria. Participants will be randomly assigned to one of two groups. One group will receive tucatinib taken orally twice daily along with intravenous trastuzumab and the mFOLFOX6 chemotherapy regimen, which includes oxaliplatin, leucovorin or levoleucovorin, and fluorouracil given by IV every two weeks. The other group will receive standard care, which could be mFOLFOX6 alone or combined with either bevacizumab or cetuximab, both given by IV on specific schedules. Treatment continues as per the study protocol. During the study, participants will be monitored for progression-free survival up to about three years using imaging reviewed by independent experts. Researchers will assess side effects and disease response. Participants must be able to provide tumor tissue samples for testing and have a good performance status. The study includes brain imaging to check for metastases and monitors safety closely throughout the treatment period.

Researchers are evaluating the safety and effectiveness of combining valemetostat tosylate with pembrolizumab compared to pembrolizumab alone in adults with advanced or metastatic non-small cell lung cancer (NSCLC) that has no actionable genomic alterations and whose tumors show high PD-L1 expression (50% or greater). This trial includes participants who have not previously received systemic therapy for their advanced or metastatic NSCLC. The study is conducted in two phases: a dose escalation phase to find the recommended phase 2 dose, followed by a dose expansion phase to further assess treatment effects. Participants receive valemetostat tosylate orally once daily until the recommended dose is established. Pembrolizumab is given as an intravenous infusion on the first day of each 21-day cycle, for up to 35 cycles. The trial compares this combination treatment to pembrolizumab alone, administered on the same schedule. The study design is open-label and randomized, allowing comparison of both treatment approaches in this patient population. During the study, participants undergo regular assessments including imaging scans to measure disease progression and safety monitoring for side effects. Researchers track dose-limiting toxicities, treatment-related adverse events, and progression-free survival over approximately 31 months. Tumor tissue samples and biomarker analyses are collected to support evaluation. Participant physical status and eligibility are carefully assessed before and during the study. Follow-up includes monitoring for safety up to 30 days after the last dose and long-term evaluation of treatment impact.

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.

Researchers are evaluating the effectiveness and safety of puxitatug samrotecan compared to the physician's choice of chemotherapy in women with advanced or metastatic endometrial cancer that expresses the B7-H4 marker. These participants have had cancer progression after treatment with platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapies. This Phase III global, open-label study aims to determine whether puxitatug samrotecan can help participants live longer without their cancer worsening or simply live longer overall, while also assessing the impact on quality of life. Participants will be randomly assigned to one of two treatment groups. One group will receive puxitatug samrotecan given by intravenous infusion at a dose of 2.4 mg/kg on Day 1 every three weeks. The other group will receive the physician's choice of chemotherapy: either doxorubicin given intravenously at 60 mg/m2 on Day 1 every three weeks, or paclitaxel given intravenously at 80 mg/m2 on Days 1, 8, and 15 in a 28-day cycle. The study plans to enroll about 700 eligible participants worldwide. During the study, participants will undergo regular assessments to monitor their cancer progression and overall survival for approximately three years. Researchers will evaluate tumor measurements using imaging and assess participants' quality of life. Safety will be closely monitored throughout the treatment period, and participants' health status will be followed to determine the effects of the treatments over time.

Researchers are evaluating the effectiveness and safety of a new treatment combination of datopotamab deruxtecan (Dato-DXd) with pembrolizumab compared to pembrolizumab alone in adults with advanced or metastatic non-small cell lung cancer (NSCLC) of non-squamous type. The study focuses on patients whose tumors have high PD-L1 expression and do not have actionable genomic alterations. This is a Phase 3 trial aiming to improve treatment outcomes for this specific lung cancer group. Participants will be randomly assigned to receive either pembrolizumab alone or Dato-DXd combined with pembrolizumab. Both treatments are given as intravenous infusions every three weeks on Day 1 of each 21-day cycle. The study includes four main periods: Tissue Screening, Screening, Treatment, and Follow-up. The treatment period continues until disease progression or unacceptable side effects occur. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, heart function tests, and biomarker evaluations from tumor tissue samples. Researchers will monitor progression-free survival and overall survival for up to approximately 44 and 71 months respectively. Safety and side effects will be closely followed throughout the study and during the follow-up period to better understand the treatments' effects over time.

Researchers are evaluating a new combination treatment of Sigvotatug Vedotin plus pembrolizumab compared to pembrolizumab alone in adults with non-small cell lung cancer (NSCLC) that has high levels of PD-L1 protein. This study focuses on participants with advanced or metastatic NSCLC (Stage 3 or 4) who have PD-L1 expression in at least 50% of their tumor cells. The purpose is to understand how well the combination works versus pembrolizumab alone as a first treatment option. All participants receive pembrolizumab through an intravenous infusion once every 6 weeks at the study clinic. Half of the participants will also receive Sigvotatug Vedotin as an intravenous infusion every 2 weeks along with pembrolizumab. Participants may continue pembrolizumab treatment for up to about two years, while those receiving Sigvotatug Vedotin can continue until their cancer no longer responds to the treatment. During the study, participants will have regular clinic visits where researchers monitor their health and response to treatment. The main outcomes measured include overall survival up to approximately two years and progression-free survival, which tracks the time until cancer worsens or death. Safety and side effects will be closely observed throughout the study period to understand the treatments' impact.

Researchers are evaluating whether combining the investigational drug mevrometostat (PF-06821497) with enzalutamide works better than enzalutamide alone in men with metastatic castration-sensitive prostate cancer (mCSPC) who have not previously received androgen receptor pathway inhibitors or chemotherapy in this setting. This Phase 3, randomized, double-blind, placebo-controlled study involves participants who have only received limited prior androgen-deprivation therapy and no evidence of disease progression before starting the study. Participants will be randomly assigned to one of two groups: one group receives oral mevrometostat together with oral enzalutamide continuously, while the other group receives a placebo with oral enzalutamide continuously. The study includes a Screening Phase, a Treatment Phase after randomization, followed by Safety Follow-up and Long-Term Follow-up periods to monitor outcomes and side effects. Throughout the study, participants will undergo regular assessments including imaging scans to evaluate disease progression, laboratory tests, and monitoring of symptoms and adverse events. The main outcome measured is Radiographic Progression Free Survival (rPFS) over approximately 4 years from randomization. Safety and long-term effects will also be monitored to understand how well participants tolerate the treatments and how the disease responds over time.