Randwick

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that kill cancer while minimizing activation of immunosuppressive cells. This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with the checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is conducted at multiple sites with regulatory and ethical approvals and includes about 115 patients. The trial has several parts: dose escalation and expansion for MDNA11 monotherapy and for its combination with pembrolizumab. MDNA11 is given intravenously every two weeks with doses adjusted to find the recommended dose for expansion. Tumor assessments using CT or MRI scans happen every 8 weeks to monitor response until disease progression or other study-end criteria occur. Treatment may continue beyond progression under certain conditions. Participants undergo evaluations including tumor imaging, laboratory tests, and safety monitoring over up to 24 months. Researchers measure recommended dose levels, treatment-related adverse events, pharmacokinetics, immune response, and anti-tumor activity such as response rates and progression-free survival. Patients can withdraw anytime, and safety follow-up continues to understand MDNA11's effects alone and with pembrolizumab.

Researchers are evaluating an investigational drug called OHB-607 to prevent Bronchopulmonary Dysplasia (BPD), a common chronic lung disease in extremely premature infants. The study compares infants receiving OHB-607 to those receiving standard neonatal care to see if the drug can reduce the incidence of severe BPD or death by 36 weeks postmenstrual age. This is a Phase 2b, randomized, open-label study involving infants born between 23 weeks 0 days and 27 weeks 6 days gestational age. Participants in the trial will be randomly assigned to one of two groups. One group will receive a continuous intravenous infusion of OHB-607 from birth until 29 weeks and 6 days postmenstrual age. The other group will receive standard neonatal care without the investigational drug. This approach allows researchers to compare the effects of OHB-607 against routine care practices for preventing lung disease in these infants. During the study, infants will be closely monitored through 36 weeks postmenstrual age and up to 24 months corrected age. Researchers will assess lung health, including the incidence and severity of BPD, time to weaning off respiratory support, and other complications such as intraventricular hemorrhage and retinopathy of prematurity. Developmental outcomes will also be measured using standardized scales at 24 months corrected age. Safety assessments and long-term follow-up are included to understand the drug's effects over time.

Researchers are evaluating calderasib, alone or combined with cetuximab, to treat advanced solid tumors in people with the KRAS G12C mutation. This phase 2, open-label study aims to learn how many patients respond to these treatments and to assess their safety and tolerability. The study is tumor-agnostic, meaning it includes various solid tumors except colorectal cancer, focusing on those that have progressed after standard treatments. Participants will be randomly assigned to receive either calderasib alone or calderasib combined with cetuximab. Calderasib is taken orally, and cetuximab is given by intravenous infusion every two weeks. There is no maximum number of treatment cycles, and participants continue treatment until they meet specific criteria for stopping. During the study, participants will be closely monitored for tumor response, adverse events, and treatment discontinuation due to side effects over up to approximately 76 months. Researchers will measure outcomes such as objective response rate, progression-free survival, duration of response, overall survival, and safety. The study begins with screening and continues with regular treatment visits and follow-ups to collect these data.

Researchers are studying the effects of NB-4746 compared with a placebo in adults with amyotrophic lateral sclerosis (ALS). The trial aims to evaluate reported side effects, how the drug is processed in the body, and changes in a blood marker called neurofilament light, which indicates nerve damage. The study includes two parts and offers an optional open-label extension for continued treatment up to one year. In Part A, participants are randomly assigned to one of three groups, receiving either a low dose or high dose of NB-4746 capsules or a placebo, taken twice daily for about one month. In Part B, participants are again randomized to receive NB-4746 at a dose determined from Part A or placebo, taken twice daily for 12 weeks. After completing Part A or B, participants may join an open-label extension to continue NB-4746 treatment for up to one year. Throughout the study, participants will have their ALS status and overall health monitored. Researchers will track side effects, safety, and tolerability from enrollment through the treatment periods. Blood tests will measure the neurofilament light levels to assess nerve damage. The trial includes regular check-ins and assessments to understand how NB-4746 affects participants over time.

Researchers are evaluating IBI354, a recombinant anti-HER2 monoclonal antibody-camptothecin derivative conjugate, in people with locally advanced unresectable or metastatic solid tumors. This Phase 1/2, open-label, multicenter study aims to assess the safety, tolerability, and dose-limiting toxicities to find the maximum tolerated or administered dose and the recommended Phase 2 dose of IBI354. The study also explores the drug's effectiveness and safety in this patient population. Participants receive sequential doses of IBI354 through a single-arm treatment plan. The study includes a Phase 1a dose escalation period to determine safety and dosing limits, followed by Phase 1b/2 periods focusing on selected solid tumors expressing HER2. Treatment schedules and dosing details are designed to monitor tolerability and explore efficacy outcomes over time. During the study, participants undergo various assessments including monitoring for adverse events, dose-limiting toxicities within the first 21 days of treatment, and evaluation of objective response rate, duration of response, progression-free survival, and overall survival for up to two years. Safety evaluations continue up to 30 days after the last dose. Participants provide written informed consent and undergo cardiac function monitoring before treatment, with ongoing evaluations throughout their participation, which lasts as long as the study and follow-up periods continue.

Researchers are studying the safety, tolerability, and how the body processes and responds to IMP1734, a PARP1 selective inhibitor, in adults with advanced solid tumors. This trial focuses on patients with recurrent or metastatic cancers such as breast, ovarian, and prostate cancer. The study aims to find the best dose and understand early effects of IMP1734 when used alone, addressing treatment options for these advanced cancers. The trial includes two parts: Part 1 involves increasing doses of IMP1734 alone to find the maximum tolerated or achievable dose. This includes patients with metastatic prostate cancer, ovarian, and breast cancer. Part 2 will explore the best dose for future studies. IMP1734 is given as oral tablets daily, except during a single-dose period. Participants may be involved for up to three years after their first treatment. During the study, participants will have regular assessments for safety including monitoring adverse events and tolerability. Researchers will evaluate pharmacokinetics (how the drug moves through the body) and pharmacodynamics (the drug's effects). They will also measure tumor response and other clinical outcomes. Follow-up will continue up to three years to monitor long-term effects and gather comprehensive data on IMP1734.

Researchers are studying the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary effectiveness of BNT3212 alone and combined with pumitamig in adults with advanced solid tumors who have no remaining standard treatment options. This first-in-human, open-label trial aims to find the recommended dose for BNT3212 both as monotherapy and in combination with pumitamig while assessing early clinical benefits. The study is conducted in multiple parts, including dose escalation and expansion phases, to carefully evaluate these factors across different tumor types. The study consists of four parts: Part A and Part B test BNT3212 alone, starting with dose escalation and then expanding to specific tumor types. Parts C and D involve escalating doses of BNT3212 combined with a fixed dose of pumitamig, followed by expansion cohorts for certain indications. Treatments are given as intravenous infusions, and participants receive escalating doses to determine the maximum tolerated dose. This stepwise approach allows gradual assessment of safety, dosing, and effectiveness while monitoring participant well-being closely. Participants will undergo evaluations including monitoring for dose-limiting toxicities within 28 days after the first dose and ongoing checks for adverse events up to 90 days after the last dose. Researchers will also measure drug levels in the blood, immune responses, and tumor responses using standardized criteria. The study monitors disease control, response duration, progression-free survival, and overall survival, with participant involvement lasting up to approximately 31 months. Safety and efficacy data will guide treatment decisions throughout the trial to balance potential benefits and risks.

Researchers are conducting a first-in-human, open-label Phase 1 trial to study D3S-003 in people with advanced solid tumors that have a specific KRAS p.G12D mutation. This early study aims to assess the safety, tolerability, how the drug moves through and affects the body, and initial signs of how well it works in this patient group. The trial includes two parts of dose escalation where participants receive D3S-003 orally either once or twice daily. This approach helps determine the best dose to use in future studies. Participants receive the study drug over treatment cycles lasting 21 days, with close monitoring for side effects and drug behavior. During the study, participants will undergo regular assessments including evaluations for side effects from screening until 30 days after the last dose, and measurement of tumor response using standard criteria. Researchers will also measure drug levels in the blood and track outcomes such as disease control and progression-free survival for up to about seven months, with careful safety monitoring throughout the trial.

Researchers are evaluating the safety and tolerability of DB-1303/BNT323 in adults with advanced or metastatic solid tumors that express HER2. This Phase 1/2a trial focuses on patients with tumors that are advanced, unresectable, recurrent, or metastatic and have limited or no standard treatment options. The study aims to identify the best dose and explore early signs of effectiveness in a variety of HER2-expressing cancers. The trial has two parts: an initial dose-escalation phase using an accelerated titration followed by a classic "3+3" design to find the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), and a dose-expansion phase to further assess safety, tolerability, and potential effects at the established dose. Participants receive DB-1303/BNT323 by intravenous infusion once every three weeks (Q3W) at various dose levels. Some groups are randomized to receive different dose levels or combinations with other drugs like Pertuzumab, Ritonavir, or Itraconazole to study drug interactions and responses. During the study, participants will have regular assessments including monitoring for dose-limiting toxicities, adverse events, and serious adverse events using standard criteria up to about one year after treatment. Researchers will also evaluate tumor responses using RECIST 1.1 criteria and collect pharmacokinetic and pharmacodynamic data. Other evaluations include heart function tests, organ function, and overall health status. The study duration varies per participant, with follow-up visits extending up to one year post-treatment to monitor safety and treatment effects.

Researchers are evaluating the safety and effectiveness of RLY-2608, a mutant-selective PI3Kα inhibitor, in adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and malformations caused by PIK3CA mutations. This Phase 2 study has three parts: a dose selection phase, an exploratory phase with various participant groups, and a randomized, double-blind study comparing RLY-2608 to placebo. The study includes multiple subpopulations to understand how the drug works across ages and conditions related to PIK3CA mutations. Participants receive oral doses of RLY-2608 tailored for their age group. Children aged 2 to under 12 undergo dose escalation to find the appropriate dose, while those 12 years and older receive fixed doses. The study has single-arm dose expansion cohorts for different age groups, followed by a randomized phase where participants aged 6 and older receive either RLY-2608 or placebo. Dosing schedules and group assignments are carefully designed to assess safety and response in various participant groups. Throughout the study, participants undergo regular assessments including lesion volume measurements, safety labs, ECGs, and evaluations of side effects. Researchers collect samples to confirm PIK3CA mutation status and monitor plasma drug levels. Patient-reported outcomes and quality of life questionnaires are also used. The main outcomes include identifying the recommended dose, tracking adverse events, and measuring changes in lesion size and symptoms over time. Participation continues with regular monitoring until study completion or discontinuation, which may last several months or longer.