A Multicenter Randomized Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of BIIB059 in Adult Participants With Active Systemic Lupus Erythematosus Receiving Background Non-Biologic Lupus Standard of Care
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study designed to evaluate the efficacy and safety of BIIB059 in participants = 18 years of age with active SLE, including joint and/or skin manifestations, who are receiving background nonbiologic lupus SOC therapy. The study will be conducted at approximately 135 sites globally. Approximately 540 participants will be randomized 1:1:1 to receive BIIB059 450 mg, BIIB059 225 mg, or placebo SC Q4W, with an additional dose at Week 2, as add-on to background nonbiologic lupusSOC therapy.The study includes a screening period of up to 4 weeks; a double-blind, placebo-controlled treatment period of 52 weeks; and an SFU period (off-treatment) of 24 weeks. Details of these different study periods are given below.
A multicenter randomized double-blind risankizumab-controlled parallel-group study to evaluate the efficacy and safety of bimekizumab in adult study participants with active psoriatic arthritis
The purpose of this research study is to evaluate the efficacy (how well something works) and safety of bimekizumab in study participants with active psoriatic arthritis (PsA) in comparison to risankizumab.
A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and PerSiStence with Inflammatory Bowel DiSease Therapy ASSIST Study
The proposed study is a multicenter, randomized, controlled, clinical trial to be conducted over 12 months. Participants in the intervention arm will verify medication adherence using the Tappt web-based system. Additionally, they will complete a two-item assessment of symptoms monthly. Participants randomized to the control group will receive standard care. All participants are required to complete questionnaires at baseline, 12 weeks, 26 weeks, and 52 weeks.
A Phase 1 Clinical Trial of CA-4948 in Combination with Gemcitabine and Nab-Paclitaxel in Metastatic or Unresectable Pancreatic Ductal Carcinoma
This phase I trial tests the safety, side effects, and best dose of emavusertib (CA-4948) in combination with gemcitabine and nab-paclitaxel in treating patients with pancreatic ductal adenocarcinoma that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). CA-4948 is in a class of medications called kinase inhibitors. It works by blocking the action of abnormal proteins called interleukin-1 receptor-associated kinase 4 (IRAK4) and FMS-like tyrosine kinase 3 (FLT3) that signal cells to multiply. This may help keep cancer cells from growing. The usual approach for patients with pancreatic ductal adenocarcinoma is treatment with chemotherapy drugs gemcitabine and nab-paclitaxel. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Giving CA-4948 in combination with gemcitabine and nab-paclitaxel may shrink or stabilize metastatic or unresectable pancreatic ductal adenocarcinoma.
A PHASE 1 FIRST IN HUMAN DOSE ESCALATION AND EXPANSION MULTICENTER STUDY OF XMT- 2056 IN PARTICIPANTS WITH ADVANCED/RECURRENT SOLID TUMORS THAT EXPRESS HER2
The proposed first-in-human study of XMT-2056 will be a Phase 1, open-label study of XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2. The XMT-2056 monotherapy trial will consist of dose escalation (DES) and expansion (EXP) parts.DES will be the dose-finding proportion of the study to assess the safety and tolerability of XMT-2056 and determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D). TheRP2D will be determined based on the totality of the clinical data, including safety and preliminary anti-tumor effect, PK, and relevant biomarker data.Upon determination of the RP2D observed in monotherapy, XMT-2056 in combination with otherapproved agent(s) may be explored (see Section 2.4.2 and Section 4.1.2) and will be specified in afuture amendment.
A Phase 1 First in human Dose Escalation and Expansion Multicenter Study of XMT-1660 in Participants with Solid Tumors
The proposed first-in-human study of XMT-1660 will be a Phase 1, open-label trial of XMT-1660 in previously treated participants with metastatic TNBC, HR+/HER2- or HER2+ breast cancer, endometrial cancer, or ovarian, fallopian tube, or primary peritoneal cancer. The study is composed of 2 parts: a dose escalation part (DES) and an expansion (EXP) part. The DES part of the study will be the dose finding cohort to assess tolerability and safety of XMT-1660 and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). The EXP part of the study will further evaluate the preliminary efficacy and safety of XMT-1660 at the MTD and/or RP2D in participants with advanced/metastatic (1) TNBC; (2) HR+/HER2- breast cancer; and (3) endometrial or ovarian, fallopian tube, or primary peritoneal cancer.
A Phase 1 Multicenter Dose Escalation and Dose Expansion Study of Antibody-Drug Conjugate MYTX-011 in Subjects with Non-Small Cell Lung Cancer KisMET-01
MYTX-011 is a cMET-targeted val-cit-monomethyl auristatin E (vcMMAE) antibody-drugconjugate (ADC) with a fully humanized immunoglobulin (Ig)G1. The drug-to-antibody ratio (DAR) for MYTX-011 is 2:1. MYTX-011 binds to cMET with high affinity and specificity. MYTX-011 has been engineered to have pH dependent binding, which results in higher internalization and payload delivery to cMET+ tumor cells. This is manifested as increased internalization in cMET+ tumor cells in vitro compared to a non-engineered parent ADC and greater in vivo efficacy in murine non-small cell lung cancer (NSCLC) cMET+ tumor xenograft models compared to reference cMET-targeting ADCs with higher DAR values. The linker/payload of MYTX-011 (vcMMAE) has been well-characterized non-clinically and/or clinically for several marketed monomethyl auristatin E (MMAE)-containing ADCs. The nonclinical and clinical toxicities of MMAE-containing ADCs also have been welldescribed- in the literature (Fisher 2021; Saber et al, 2015).Preliminary safety and efficacy data from in vitro and in vivo nonclinical assessments of MYTX-011 further support development as a treatment for NSCLC in appropriately designed clinical research studies.The study will be conducted in 2 parts. Part 1 will assess the safety and tolerability of MYTX-011 and identify the dose to be studied in Part 2. Part 2 will include subjects with NSCLC with CMET overexpression or MET amplification/exon 14 skipping mutations, populations with a current unmet medical need
A Phase 1 Multicenter Open-Label Study Of CC-97540 (BMS-986353) CD19-Targeted Nex-T Chimeric Antigen Receptor (CAR) T Cells in Participants with Severe Refractory Autoimmune Diseases: Systemic Lupus Erythematosus Idiopathic Inflammatory Myopathy or Systemic Sclerosis
SLE disease activity results in accumulation of tissue and organ damage (eg, nephritis, multisystem organ failure, and central nervous disease) that contributes to morbidity and premature death. In addition to increased risk of mortality, SLE may have a profound effect on quality of life, with fatigue, pain, and disease flares contributing to disability. Despite extensive efforts to develop novel therapies for SLE, there remains an unmet need for novel therapies, particularly for treatment refractory patients and those who suffer from acute and long-term treatment-related toxicities, including recurrent infections, osteoporosis, accelerated cardiovascular disease, and infertility. Failure to respond and/or achieve a complete clinical response following treatment with systemic glucocorticoids and 2 or more immunosuppressive drugs indicates refractory disease with a poor overall prognosis and little expectation of achieving remission. New treatments for such severe, refractory cases are urgently needed.This study will enroll participants with SLE who have a severe, life-threatening disease course and have been refractory to currently available therapies. Because of the recognized pathogenic role of autoreactive B cells and plasmablasts in patients with SLE, the current study will explore the potential utility of depletion of CD19+ B cells and plasmablasts with CD19-specific CAR T cells in this dose-ranging study to achieve deep and sustained elimination of autoreactive B cells and plasmablasts, inducing disease remission and potentially restoring humoral immune tolerance. The present study aims to establish the tolerability and preliminary efficacy of the leukapheresis, lymphodepletion and infusion of the study intervention, CC-97540, as well as the pharmacokinetics of CC-97540, and depth and duration of B cell depletion.
A Phase 1 Open-Label Multicenter Study to Assess the Safety Tolerability Pharmacokinetics and Anti-tumor Efficacy of DZD6008 in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR Mutation (TIAN-SHAN1)
This is a phase 1 study testing a new medicine called DZD6008 (an EGFR inhibitor) in patients with lung cancer with EGFR mutation. This study has two parts. In part one, the study medicine DZD6008 will be given in different doses to small groups of patients. The study team will gradually increase the dose to find the dose that works well and has fewer side effects. In part two, patients will be divided into two groups to receive two different doses of the study medicine that worked well in the first part of the study. All patients will be closely monitored for side effects and discomfort throughout the study. Patients will have blood samples taken to see how well their body is handling the medicine and how the medicine is changing their cancer. Doctors will examine the special scans of all patients to see how the study medicine changes the tumor size and make sure the patients are doing well. Patients will be followed up for 28 + 7 days after the last dose.
A Phase 1 Open-label Preliminary Pharmacokinetics (PK)and Safety Study of CLN-049 (An fms-like tyrosine kinase 3 [FLT3] x cluster of differentiation 3 [CD3] bispecific T cell engager) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
A Phase 1, Open-label, Preliminary Pharmacokinetics (PK)and Safety Study of CLN-049 (An fms-like tyrosine kinase 3 [FLT3] x cluster of differentiation 3 [CD3] bispecific T cell engager) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)