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Researchers are evaluating the safety and tolerability of amivantamab, an investigational drug, in patients with high grade malignant brain tumours such as glioblastoma. This Phase 1b trial focuses on a biomarker-defined group of patients whose tumours show EGFR amplification. The study aims to determine the preliminary anti-tumour activity of amivantamab administered at the recommended Phase 2 dose, with decisions guided by adaptive trial design and safety review committees. Amivantamab will be given by intravenous infusion weekly for the first 4 weeks, then every 2 weeks thereafter until the disease progresses or unacceptable side effects occur. The initial dose is split over two days, with subsequent doses given over 2 to 5 hours initially and shorter infusions if well tolerated. This Phase 1b biomarker arm will enroll 12 patients with relapsed glioblastoma to assess treatment effects. Participants will undergo regular monitoring including whole genome and transcriptome data collection as part of the Minderoo Precision Brain Tumour Programme. Safety and tumour response will be closely assessed through clinical evaluations and imaging over an 18-month period. The main outcomes measured are safety, tolerability, and preliminary anti-tumour activity, with additional analysis of molecular markers related to treatment response.

Researchers are evaluating the safety, tolerability, and preliminary antitumor activity of paxalisib combined with temozolomide in patients with high-grade malignant brain tumors, including glioblastoma. This Phase 1b and Phase 2 study is part of the 5G-PEARL trial, which uses biomarker-guided approaches to treat tumors with specific genetic changes such as PI3K mutations or PTEN loss. The study aims to test these treatments in molecularly defined patient groups to better understand their effects. The study includes two parts Phase 1b focuses on safety and early activity, while Phase 2 assesses effectiveness further. In Phase 1b, patients receive paxalisib starting at 45 mg once daily, with a possible increase to 60 mg per day in Cycle 2. Temozolomide is taken orally once daily on days 1 to 5 of each 28-day cycle, starting at 150 mgm2 with potential dose increase to 200 mgm2 from Cycle 3 if tolerated. The trial enrolls patients into two biomarker arms based on tumor genetics, with adaptive decision points to guide study progress. Participants will have assessments including safety monitoring and genetic biomarker analysis over up to two years, depending on the phase. Researchers measure treatment-emergent adverse events and antitumor activity as primary outcomes. Quality of life and additional biomarker responses are also evaluated. Patients will be monitored regularly through clinical visits and tests to track treatment effects and side effects throughout the study duration.

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of two investigational drugs, avutometinib and defactinib, in patients with high grade malignant brain tumours, including glioblastoma GBM. This Phase 12 clinical trial uses biomarker-guided approaches to target specific molecular subtypes of brain tumours. The study is part of the Minderoo 5G platform and includes patients with relapsed or frontline minimal residual disease MRD settings. In Phase 1b, patients with relapsed GBM will receive oral avutometinib at a dose of 3.2 mg twice weekly and defactinib at 200 mg twice daily after meals, aiming for a total weekly dose of 6.4 mg and daily dose of 400 mg respectively. Phase 2 will test the antitumour activity of these drugs given at the recommended dose, either as a doublet or combined with temozolomide, depending on earlier results. Treatment will be given in molecularly defined biomarker arms, with decisions guided by safety and efficacy data. Participants will undergo assessments for safety, tolerability, and tumour response over 9 to 12 months. Molecular profiling will help identify response markers, and quality of life will be monitored during Phase 2. Patients must consent to genomic testing and will be followed regularly with clinical evaluations. The study includes rigorous monitoring for side effects and disease progression, with a total participation duration aligned with treatment phases and follow-up.

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

Researchers are exploring new treatments for women with relapsed high-grade serous ovarian cancer, which is a fast-growing cancer starting in ovarian cells, the lining of the belly, or fallopian tubes. The study evaluates raludotatug deruxtecan R-DXd, a type of antibody drug conjugate, combined with other therapies, to understand safety, tolerability, and cancer response. This includes women with platinum-sensitive and platinum-resistant recurrent ovarian cancer who have had prior treatments. The study has two parts Part 1 involves gradually increasing doses of R-DXd combined with chemotherapy drugs like carboplatin, paclitaxel, bevacizumab, or pembrolizumab to find a recommended dose. Part 2 uses this recommended dose to further assess treatment effects. Participants receive intravenous infusions every three weeks, with chemotherapy cycles lasting up to about four months and pembrolizumab up to two years. The combinations vary depending on cancer sensitivity and treatment history. Participants undergo regular treatment visits where cancer response and side effects are monitored. Tumor tissue samples are collected before treatment. Researchers track adverse events, dose-limiting toxicities, and how long the cancer responds to treatment. The study lasts up to approximately three years, allowing for long-term safety and effectiveness assessments, with ongoing evaluation of participants health throughout the trial.

Researchers are evaluating the safety, efficacy, and optimal dosing of a combination of two investigational treatments, BNT323 trastuzumab pamirtecan and BNT327 pumitamig, in people with advanced breast cancer. This includes those with hormone receptor-positive or -negative, HER2-positive, HER2-low, HER2-ultralow, HER2-null breast cancer, or triple-negative breast cancer. The study is a Phase III multi-site, open-label trial with a focus on advanced breast cancer treatment options. The study has two parts. Part 1 involves dose escalation of BNT323 combined with BNT327 to determine the recommended Phase 2 dose using six different dose levels. Part 2, which begins after Part 1 completion, includes dose optimization and exploratory cohorts. Cohort 1 in Part 2 uses randomization into four treatment arms, including combination therapy at different doses and monotherapies of either BNT323 or BNT327. Other cohorts receive the recommended dose without randomization. Participants will undergo assessments including tumor scans and cardiac function tests, with monitoring for side effects and tumor response up to 36 months. Researchers will track dose-limiting toxicities and treatment-emergent adverse events during early treatment cycles and monitor objective response rates and disease control over time. Safety and efficacy data will be collected through scheduled visits and tumor assessments during and after treatment to evaluate the study drugs effects and tolerability.

Researchers are evaluating new treatment combinations involving BNT314 and pumitamig alongside chemotherapy in people with metastatic colorectal cancer mCRC that is microsatellite stable or mismatch repair proficient. This study includes three parts Part A focuses on safety and dose escalation of BNT314 with pumitamig Part B assesses safety and dosing of BNT314 combined with pumitamig and standard chemotherapy in treatment-nafve or previously treated patients Part C tests effectiveness of these combinations compared to usual chemotherapy treatments. The study aims to see if these treatments can shrink tumors or slow cancer growth. Participants receive intravenous infusions of BNT314 and pumitamig, along with standard of care SoC chemotherapy, in various dose levels and combinations depending on the study part. Part A evaluates up to five dose levels of BNT314 and one or two doses of pumitamig. Part B uses optimized doses of BNT314 with pumitamig and one of two chemotherapy regimens. Part C compares the recommended BNT314 and pumitamig doses plus chemotherapy against other treatment combinations, including bevacizumab with chemotherapy or pumitamig with chemotherapy. Treatment continues until disease progression, intolerance, withdrawal, or study end. Participants undergo eligibility screening, then receive treatment for an average of 6 to 10 months. They are regularly monitored for safety and treatment effects, including tumor response and side effects, with assessments extending up to 57 months after starting treatment. After treatment ends, participants enter safety follow-up and long-term survival monitoring to track any lasting effects and overall outcomes. Randomization is used in Parts B and C to assign treatments by chance.

Researchers are evaluating the safety, effectiveness, optimal dose, and behavior of an investigational drug called BNT326, alone or combined with other immunotherapy agents, in adults with advanced solid tumors. This study includes patients with tumors that have either spread metastatic, returned after treatment, or progressed despite previous therapies, across various cancer types such as melanoma, lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer. Participants are divided into two parts Part 1 tests BNT326 alone in different tumor-specific groups, some with dose randomization to find optimal dosing. Part 2 evaluates BNT326 alone or combined with another investigational drug called pumitamig in several cancer types, with some groups receiving randomized doses and others non-randomized treatments. Treatments are given via intravenous infusion, with some oral medications combined in Part 1. The study includes dose escalation and randomization phases, and treatment can continue for up to 24 months or until disease progression or other reasons. During the study, participants undergo screening, treatment, safety follow-up, efficacy follow-up, and long-term survival monitoring phases. Researchers assess adverse events, treatment responses, disease progression, and drug behavior in the body using clinical evaluations and laboratory tests. Follow-up assessments occur up to approximately 38 months for Part 1 and 48 months for Part 2, with continued treatment possible for those benefiting from the therapy. The study aims to gather comprehensive data on safety, dosing, and effectiveness in this patient population.

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

Researchers are investigating a combination therapy of BNT326 and pumitamig also called BNT327 or PM8002 in adults with advanced or metastatic non-small cell lung cancer NSCLC who may have relapsed, progressive, or treatment-nafve disease. This multi-site, open-label study aims to find the best dose levels for this combination, assess how well participants tolerate the therapy, including side effects, and evaluate its ability to shrink tumors in this population. The study has three parts Part 1 focuses on finding safe dose levels for the combination Part 2a expands the dose evaluation to assess preliminary effectiveness and safety Part 2b is a randomized phase to optimize doses and understand the contribution of each drug component. Participants will receive intravenous infusions of BNT326 and pumitamig or pumitamig alone in some arms. Treatment continues until disease progression, unacceptable side effects, withdrawal, study end, or up to 24 months. Dose levels for later parts are chosen based on earlier safety and efficacy data. Participants will go through screening, treatment, safety follow-up, efficacy follow-up, and long-term survival follow-up phases, with total involvement expected to last about 36 months unless treatment benefit continues. Assessments include monitoring for dose-limiting toxicities, adverse events, tumor response, progression-free survival, overall survival, and pharmacokinetics of the drugs. Safety evaluations continue up to 90 days after treatment ends, and antibody responses to the drugs are also measured for up to one year post-treatment.