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Researchers are evaluating amivantamab, an investigational drug, in patients with high-grade malignant brain tumors, specifically glioblastoma multiforme (GBM) and related molecular subtypes. This Phase 1b trial aims to assess the safety, tolerability, and preliminary antitumor activity of amivantamab when given at the recommended Phase 2 dose. The study is part of the Minderoo 5G platform, focusing on biomarker-guided therapies for patients with molecularly defined brain tumors characterized by EGFR amplification and other genetic markers. Amivantamab is given as an intravenous infusion weekly for the first 4 weeks, followed by every 2 weeks until disease progression or unacceptable side effects occur. The initial dose is split over two days to improve tolerance, starting with 350 mg over 4 hours and then 1400 mg over 6 hours. Subsequent doses are 1750 mg over 2-5 hours in the first cycle and 2-3 hours thereafter if well tolerated. The trial includes an adaptive design with decision points led by a Safety Review Committee to guide further study steps and progression to Phase 2 depending on emerging data. Participants will undergo regular evaluations including clinical assessments, laboratory tests, and imaging to monitor tumor response and safety over an 18-month period. Researchers will measure safety outcomes and preliminary efficacy using established criteria for tumor response. Patients must meet specific eligibility criteria related to diagnosis, previous treatments, and general health status. The study also includes monitoring for side effects and adherence to study protocols throughout participation.

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of paxalisib combined with temozolomide in patients with high grade malignant brain tumours, specifically glioblastoma. This Bayesian multi-centre, multi-arm, open-label, adaptive Phase 1/2 trial focuses on molecularly defined biomarker arms, including patients with hyperactivating PI3K mutations or PTEN loss. The study aims to provide proof-of-concept molecular hypothesis testing within the 5G platform for patients with these aggressive brain tumours. During Phase 1b, patients will be treated with paxalisib starting at 45 mg once daily, with an option to increase the dose in the second cycle. Temozolomide will be given orally once daily on days 1 to 5 of a 28-day cycle, starting at 150 mg/m2 with possible escalation to 200 mg/m2 after the second cycle if well tolerated. Each biomarker arm will enroll 10 patients in parallel during Phase 1b, with up to 32 patients recruited across Phase 1b and Phase 2 if initial safety and efficacy decisions support continuation. Participants will undergo regular monitoring for safety and antitumour activity over 12 months in Phase 1b and up to 24 months in Phase 2. Assessments include clinical evaluations, biomarker analysis, and imaging to measure treatment effects. The study emphasizes tracking adverse events, tolerability, and tumour response to the investigational combination therapy, with ongoing review by a Safety Review Committee to guide study progression and patient safety.

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of the investigational drugs avutometinib and defactinib in patients with malignant brain tumors, specifically glioblastoma and other molecularly defined high-grade brain tumors. This Phase 1/2 trial is part of the Minderoo 5G platform and includes biomarker-guided treatment arms targeting tumors with specific genetic features such as hyperactivating BRAF mutations or NF1 loss. The study uses a Bayesian multi-arm, open-label, adaptive design for efficient hypothesis testing and patient assignment. In the Phase 1b portion, patients with relapsed glioblastoma multiforme (GBM) receive double therapy with oral avutometinib at 3.2 mg twice weekly (total 6.4 mg per week) and oral defactinib at 200 mg twice daily (total 400 mg per day). Treatment arms progress to Phase 2 upon meeting predefined success criteria, where efficacy is tested in the front-line minimal residual disease setting. Phase 2 may involve doublet therapy or triplet therapy adding temozolomide capsules, given either concurrently or sequentially based on emerging data and safety review committee decisions. Participants undergo screening and assessments including molecular tumor profiling, neurological evaluations, and laboratory tests before and during treatment. Researchers monitor safety, tolerability, and tumor response over 9 to 12 months depending on the phase. The trial includes ongoing safety reviews and adaptive decision points to guide treatment continuation or modification. Participant involvement includes oral medication administration, clinical follow-up, and data collection on tumor activity and side effects throughout the trial duration.

Researchers are evaluating new treatment options for women with relapsed high-grade serous ovarian cancer, a fast-growing cancer that starts in the cells covering the ovaries, lining of the belly, or fallopian tubes. This study focuses on people whose cancer has returned after prior platinum-based chemotherapy. The goal is to assess the safety, tolerability, and effectiveness of a new antibody drug conjugate called raludotatug deruxtecan (R-DXd), alone or combined with other anticancer treatments, in this patient group. The study has two parts: Part 1 is a dose escalation phase to find the recommended dose of R-DXd, and Part 2 is an expansion phase using that dose. R-DXd is given as an intravenous infusion on Day 1 of every 3-week cycle. Other treatments that may be given include carboplatin and paclitaxel (each up to 6 cycles), bevacizumab every 3 weeks, pembrolizumab up to 35 cycles, gemcitabine on Days 1 and 8 of each 3-week cycle, and pegylated liposomal doxorubicin every 4 weeks. Rescue medications to control side effects are also administered according to protocol. Participants will be monitored for adverse events, dose-limiting toxicities, and treatment discontinuations up to about 3 years. Researchers will measure cancer response using established criteria and assess safety through clinical exams, imaging, and laboratory tests. Eligibility includes having measurable disease and adequate health status. The study includes long-term follow-up to track treatment effects and safety outcomes over time.

Researchers are conducting a Phase I/II, multi-site, open-label study to evaluate the safety, effectiveness, and optimal dosing of the investigational treatments BNT323 combined with BNT327 in adults with advanced breast cancer. This includes those with hormone receptor-positive or negative types, HER2-positive, HER2-low, HER2-ultralow, HER2-null breast cancer, or triple-negative breast cancer. The study aims to understand how these treatments work alone and together in this patient population. The study has two parts: Part 1 involves dose escalation where participants with chemotherapy-pretreated advanced breast cancer receive BNT323 and BNT327 together to find the recommended Phase 2 dose. Part 2 is an expansion phase that tests the safety and effectiveness of the chosen dose, including randomized comparisons of combination therapy at different doses and monotherapies. Participants may be assigned to one of four treatment arms, with dosing administered via intravenous infusion. Participants will be monitored for dose-limiting toxicities during the first 21 days of treatment, as well as adverse events up to 90 days after the last dose. Tumor response will be assessed for up to 36 months. Evaluations include heart function tests, tumor imaging, safety assessments, and tracking of side effects. The study carefully monitors treatment safety, effectiveness, and participant health throughout the trial duration.

Researchers are evaluating the safety and effectiveness of new treatments called BNT314 and BNT327 combined with chemotherapy for people with metastatic colorectal cancer (mCRC) that is microsatellite stable or mismatch repair proficient (MSS/pMMR). This study includes participants who did not respond well to their first chemotherapy treatment and aims to find the right dose and assess how well these treatments work together to shrink tumors or slow their growth. The study includes multiple phases to test safety, dosing, and treatment benefits. The study has three parts: Part A focuses on safety and dose escalation of BNT314 with BNT327; Part B tests the safety and optimal dose of BNT314 combined with BNT327 and standard chemotherapy; and Part C compares the combination treatment with standard chemotherapy alone to see if it improves outcomes. Treatments are given by intravenous infusion or oral methods depending on the drug. Participants receive treatment until their disease worsens, they cannot tolerate the therapy, or the study ends, with an average treatment duration of 6 to 10 months. Participants will be screened, treated, and followed up for safety and long-term survival. Researchers will regularly monitor for side effects, treatment response, and disease progression using scans and laboratory tests. The study includes a safety follow-up period and a long-term survival follow-up that can last up to 57 months, with committees overseeing participant safety throughout the trial.

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes (pharmacokinetics) an investigational drug called BNT326. This study includes people with advanced solid tumors that are metastatic, recurrent, or have progressed after previous treatments. The investigation is divided into two parts: Part 1 tests BNT326 alone, and Part 2 studies BNT326 alone or combined with other immunotherapy drugs, including pumitamig (BNT327). Participants have specific tumor types like melanoma, non-small cell lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer, among others. In Part 1, participants receive BNT326 by intravenous infusion in various groups based on cancer type and prior treatments. Part 2 involves BNT326 given alone or with pumitamig, also by intravenous infusion, in several defined cancer groups. Some groups are randomized to receive different dose levels or combinations to find the optimal treatment plan. The study includes a screening phase, treatment phase lasting up to 24 months or until progression or unacceptable side effects, a safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 38 months for Part 1 and 48 months for Part 2. During the study, participants undergo regular assessments including measuring tumor response using RECIST criteria, monitoring for side effects and serious adverse events up to months after treatment ends, and measuring drug levels in the blood. Researchers track treatment interruptions or discontinuations due to side effects and evaluate dose-limiting toxicities. Tumor tissue samples are required before enrollment. Safety and effectiveness data are collected throughout treatment and follow-up periods to understand how well BNT326 works alone or combined and its safety profile.

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 a combination treatment using BNT326 and BNT327 in adults with advanced or metastatic non-small cell lung cancer (NSCLC), including those with relapsed, progressive, or treatment-nafve disease. This multi-site, open-label study includes dose-finding and dose-expansion phases to investigate the safety, tolerability, and preliminary effectiveness of this combination therapy. The study targets patients whose tumors are advanced, metastatic, or recurrent with no curative treatment options available and includes participants with different genomic alterations. The study is divided into several parts: Part 1 is a dose escalation phase to find safe dose levels of BNT326 with BNT327; Part 2a expands the dose to further evaluate safety and initial efficacy; Part 2b focuses on dose optimization and understanding the contributions of each component. Participants receive intravenous infusions of BNT326 and BNT327, with some cohorts possibly receiving additional treatments such as pembrolizumab or standard chemotherapy. Treatment continues until disease progression, unacceptable side effects, withdrawal, or a maximum of 24 months. Dose levels for certain cohorts are determined based on earlier phase data, and some parts include randomization to different treatment groups. Participants undergo a screening period before starting treatment, followed by treatment, safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 36 months. Researchers assess dose-limiting toxicities within the first 21 days of treatment and monitor adverse events, treatment interruptions, and objective response rates up to 36 months. Tumor measurements, safety labs, imaging, and patient health status are regularly evaluated. The study tracks tolerability and efficacy while ensuring participant safety throughout treatment and follow-up.

Researchers are evaluating the safety and potential benefits of the investigational drug BNT329 for people with advanced solid tumors that express the tumor marker CA19-9. This Phase I/IIa study aims to find the best dose of BNT329 by tracking side effects and their severity. It also explores how well the drug works by measuring participants' tumor responses and how long the tumor stays controlled. Additionally, the study examines how BNT329 moves through and affects the body. The trial has up to four parts (A, B, C, and D). Parts A, B, and C focus on increasing doses to assess safety and tolerability in participants with various advanced cancers expressing CA19-9, including pancreatic, bile duct, bladder, colorectal, gastroesophageal junction, endometrial, and ovarian cancers. Part B tests a more frequent dosing schedule, and Part C tests pre-treatment with a CA19-9-targeting monoclonal antibody before BNT329. Part D evaluates safety and early signs of effectiveness in pancreatic cancer patients who have had prior treatments. Participants receive BNT329 through intravenous infusion. Parts A, B, and C are non-randomized, while Part D randomizes participants to two different dose levels. Participants go through screening, treatment lasting up to two years, end-of-treatment visits, two safety follow-ups, and survival monitoring until death, withdrawal, or study end. Researchers monitor side effects, serious adverse events, dose changes due to side effects, and tumor response rates over time, with follow-up periods lasting up to 36 months. Safety assessments continue up to 60 days after the last dose, and long-term survival is tracked throughout the study.