A Phase 3 Two-stage Randomized Multi-center Controlled Open-label Study Comparing Iberdomide Maintenance to Lenalidomide Maintenance Therapy after Autologous Stem Cell Transplantation (ASCT) in Participants with Newly Diagnosed Multiple Myeloma (NDMM)
This is a two-stage, Phase 3, randomized, multi-center, controlled, open-label study comparing iberdomide maintenance to lenalidomide maintenance therapy after ASCT in participants with newly diagnosed multiple myeloma.The primary objective of this study is to compare the efficacy of iberdomide to that of lenalidomide maintenance after ASCT in participants with NDMM, as measured by PFS.
A PHASE I FIRST-IN-HUMAN OPEN-LABELTRIALTO INVESTIGATE THE SAFETY TOLERABILITY PHARMACOKINETICS AND PRELIMINARY ANTITUMOR ACTIVITY OF SIM0500 A HUMANIZE GPRC5D-BCMA-CD3 TRISPECIFIC ANTIBODY IN PARTICIPANTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA
This is a clinical trial that aims to test the effectiveness and how the body processes a drug called SIM0500 in adult patients with relapsed or refractory multiple myeloma (RRMM). The trial has two parts: Part 1 focuses on finding the right doses (dose escalation), and Part 2 looks at optimizing those doses. In both parts, patients will receive SIM0500 until their disease worsens, they experience severe side effects, they decide to stop, or the trial ends. In Part 1, researchers will start with a low dose of 0.15 µg/kg and may lower it to 0.05 µg/kg if patients have serious side effects. The treatment will be given once a week, and each treatment cycle will last 28 days.
A Phase I Multicenter Open-label First-in Human Dose Escalation and Expansion Study of AZD9592 as Monotherapy and in Combination with Anti-cancer Agents in Patients with Advanced Solid Tumors
This is a first-in-human modular Phase 1, open-label, multi-center study to evaluate the safety and tolerability and identify a recommended phase 2 dose (RP2D) of AZD9592 alone and with a specific combination treatment, in EGFR and cMET expressing tumors, initially NSCLC EGFR mut (L858R/ex19del) and wild type, as well as HNSCC. The study will also evaluate the preliminary efficacy, PK, PD and immunogenicity of AZD9592.
A phase I open-label multi-center study of KFA115 as a single agent and in combination with pembrolizumab in patients with select advanced cancers
This study is a FIH, open-label, phase I, multi-center study that consists of two treatment arms in dose escalation: single-agent KFA115 (Arm A escalation) and KFA115 in combination with pembrolizumab preceded by a KFA115 run-in for 1 cycle (Arm B escalation). In expansion, the study consists of three treatment arms: single-agent KFA115 (Arm A expansion), KFA115 in combination with pembrolizumab after single-agent KFA115 run-in (Arm B expansion), and KFA115 to be initiated with pembrolizumab concurrently (Arm C expansion).
A PHASE I RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED SINGLE-CENTER STUDY OF SAFETY AND EFFECTIVENESS OF INNATE IMMUNITY STIMULATION VIA TLR9 IN MILD COGNITIVE IMPAIRMENT OR EARLY AD
This single-center, double-blind, placebo-controlled study will recruit in total 39 participants with either Mild Cognitive Impairment due to Alzheimer’s disease (MCI) or Mild Alzheimer’s disease dementia (mild AD). There will be 3 Dose levels. An initial cohort of 13 subjects will be randomized to a Dose level 1 (0.1 mg/kg vs. placebo) lasting 8 weeks. An additional 13 subjects will be recruited and randomized into Dose level 2 (0.25 mg/kg vs. placebo) for 8 weeks and 13 subjects for the last Dose level 3 (0.5 mg/kg vs. placebo) for 8 weeks. Primary ObjectivesEvaluate the safety and tolerability of 3 escalating dose levels of CpG 1018 (dose level 1: 0.1 mg/kg vs. placebo; dose level 2: 0.25 mg/kg vs. placebo; dose level 3: 0.5 mg/kg vs. placebo) as 3 subcutaneous (s.c.) injections in patients with MCI or mild AD.Secondary ObjectivesKey secondary objectives:• To evaluate drug effect on immunostimulatory responses• To evaluate drug effect on disease progression An independent unblinded Data Safety Monitoring Board (DSMB) will convene at regular intervals to monitor the overall safety of the study and to make recommendations to the PI related to study safety as appropriate.
A PHASE I/IB SINGLE ARM STUDY OF TWO FRACTION SBRT WITH DOMINANT LESION SIB FOR THE TREATMENT OF LOCALIZED PROSTATE CANCER
Phase I/IB, single arm trial of Two-Fraction SBRT with an MRI directed, dominant intraprostatic lesion, simultaneous integrated boost based on genomic classification in the treatment of localized prostate cancer. Primary endpoint will be physician-reported grade 2 or higher CTCAE toxicity. Secondary endpoints are: EPIC quality of life, PSA Nadir, and Phoenix Definition Biochemical failures as well as Disease Free Survival, Overall Survival, and MFS.
A Phase I/IIa Open-label Multi-centre Study to Assess the Safety Tolerability Pharmacokinetics and Preliminary Efficacy of AZD0022 Monotherapy and in Combination with Anti-cancer Agents in Participants with Tumours Harbouring a KRASG12D Mutation (ALAFOSS-01)
This study is a trial to test the tolerability, side effects, and early effectiveness of the drug AZD0022 in patients with advanced tumors that have a KRAS G12D mutation. The trial has three parts. In Part A, doctors will find the highest dose of the drug that causes few side effects. In Part B, they will figure out the best dose to use from part A. In Part C, they will see how well the drug works against cancer. The main goals are to see how many side effects happen, how well the drug works, and how the drug acts in the body.
A PHASE IB STUDY TO ASSESS SAFETY OF CONCURRENT AZELIRAGON WITH CRANIOSPINAL IRRADIATION IN PATIENTS WITH LEPTOMENGINAL METASTASIS FROM SOLID TUMOR MALIGNANCIES OR HIGH-GRADE GLIOMAS
This study is a Phase 1b clinical trial at a single hospital to test the tolerability and safety of combining the drug Azeliragon with craniospinal irradiation (CSI) in patients with leptomeningeal metastasis from solid tumors or high grade gliomas. Patients will take Azeliragon for 7 days before starting CSI, continue it during CSI, and take it for 7 more days afterward. The study will test different doses to find the highest dose of Azeliragon that is tolerated with CSI, based on any issues during the first 4 weeks of treatment. Once the best dose is found, additional patients will be treated at that level. Patients will have regular check-ups, including brain and spine MRIs and spinal fluid tests, during treatment and at 4 weeks, 3 months, 6 months, 9 months, and 12 months after finishing CSI. The study will also track survival, disease progression, and patient-reported symptoms. Patients can continue other treatments, like chemotherapy or immunotherapy, after finishing radiation, and their progress will be followed until death
A Phase Ib trial to assess the effects of belzutifan on 89Zr-DFO-girentuximab uptake as a surrogate to determine CAIX tumor expression in patients with clear cell Renal Cell Carcinoma
The treatment landscape of advanced clear cell RCC has been transformed over the past few years. The development of combinations of dual check point inhibitors (CPIs) targeting CTLA-4 and PD-1 (ipilimumab/nivolumab) and immunotherapy/tyrosine kinase inhibitors (TKI) have demonstrated a clear survival benefit over TKI alone in the first line setting.[1-4] Despite the clear advancement in the field there is still a significant number of patients who have either primary refractory disease or develop acquired resistance during therapy with disease progression and eventually succumb to the disease (ORR: 45% to 70%, progression-free survival: 11.6-23.9 months). Belzutifan, a hypoxia inducible factor-2 (HIF-2) inhibitor is currently FDA approved for patients with germline Von-Hippel Lindau (VHL) syndrome and in patients with relapsed RCC who have progressed on CPI and a vascular endothelial factor (VEGF) TKI. The latter approval was based on improved PFS benefit of belzutifan vs everolimus in this disease setting (18 month PFS 22.5% vs 9%).[5] Nevertheless, treatment resistance to belzutifan is inevitable and new approaches are needed to improve the durability of response to belzutifan. Here, we propose to evaluate the effect of belzutifan on carbonic-anhydrase IX (CAIX) expression using 89Zr-deferoxamine (DFO) - girentuximab PET in a prospective clinical trial to lay the foundation of a novel combination treatment strategy with future CAIX targeted agents.Through its inhibition of HIF2, Belzutifan leads to fundamental changes in cell signaling downstream of VHL. VHL mutation is the main driver of RCC tumorigenesis through constitutive stabilization of HIFs which then promote the transcription of several key genes involved in tumorigenesis and progression. [6] HIF1 and HIF2 are the key HIF isoforms and have distinct roles in the pathogenesis of RCC.[7] HIF-1a is also implicated in the expression of CAIX, a metalloprotease involved in pH regulation.[8, 9] This is clinically relevant as CAIX PET is an emerging diagnostic agent and therapeutic target for RCC. Previously, downregulation of HIF-2a in vitro has been shown to lead to overexpression of HIF-1a in tumor cells[7] and thus increased CAIX expression in preclinical models. We hypothesize that belzutifan treatment, by suppressing HIF-2a, will lead to increased HIF1 transcriptional activity thereby increasing CAIX expression.We aim to identify changes in CAIX expression induced by HIF-2a inhibition by initiating belzutifan single agent therapy and imaging CAIX expression with 89Zr-DFO-girentuximab PET before and 4 weeks after initiating treatment. This will be the first study to evaluate potential changes in CAIX expression altered by belzutifan. Information gained from this study will be leveraged to develop combinations of belzutifan with CAIX targeted agents including radioimmunotherapy in the future.
A Phase Ib/III Open-label Randomised Study of Capivasertib plus CDK4/6 Inhibitors and Fulvestrant versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced Unresectable or Metastatic Breast Cancer (CAPItello-292)
This is a Phase Ib/III, multicentre study of capivasertib plus CDK4/6i (palbociclib, ribociclib or abemaciclib) and fulvestrant, for the treatment of participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following either recurrence orprogression on, or after (neo)adjuvant ET. The study comprises two parts (Phase Ib and Phase III); the recommended Phase III doses (RP3Ds) of capivasertib and CDK4/6i in combination with a fixed dose of fulvestrant will be determined in the open-label, dose findingPhase Ib part. The efficacy and safety of the capivasertib arm will be compared to the control arm in the randomised, open-label Phase III part.The Phase Ib part of the study consists of an open-label, 3-arm dose finding phase to determine the safe and well tolerated doses and schedules (RP3D) of capivasertib plus CDK4/6i (palbociclib, ribociclib, or abemaciclib) and fulvestrant (the latter administered atfixed dose and schedule, as per label) as triplet combinations in participants with ABC. The maximum tolerated doses (MTD) may also be determined.The Phase III part is an open-label, randomised study assessing the efficacy of the capivasertib arm (capivasertib plus investigator’s choice of CDK4/6i [palbociclib or ribociclib] and fulvestrant) versus the control arm (investigator’s choice of CDK4/6i [palbociclib orribociclib] and fulvestrant) for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after endocrine therapy. The Phase III doses of capivasertib, palbociclib, and fulvestrantcombination and capivasertib, ribociclib, and fulvestrant combination were identified in the Phase Ib part of this study, based on the safety and tolerability data that were reviewed and endorsed by an external Safety Review Committee (SRC). Abemaciclib is not planned to beincluded among the Phase III CDK4/6i options due to an increasing global preference for ribociclib and the anticipated increasing use of abemaciclib in the adjuvant setting.