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 CB-010 a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy in Patients with Relapsed/Refractory B Cell Non-Hodgkin Lymphoma (ANTLER)
T cells are an integral part of the immune system that kills cancer cells in thebody. T cells have been harvested from peripheral blood and modified toexpress chimeric antigen receptors (CARs) to direct their antitumor activitytoward malignant cells. Despite their clinical benefits, autologous CAR-T celltherapies present barriers for some patients because of insufficiencies in patientT cells. In contrast, allogeneic CAR-T cells may offer a significant benefit topatients who are ineligible for autologous CAR-T cell products, patients whomay be at risk for manufacturing failure of their cells, patients with insufficientT cells for product manufacture, patients refractory to treatment, or those forwhom bridging therapy may deteriorate performance status. CB-010 is aproduct of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing designed to create a human T cell product with specificcapacity to target diseased B cells and to function in an environment of intrinsicimmunosuppression to treat disease. This approach to cancer therapy aims toprovide treatment for patients with limited treatment options forrelapsed/refractory (r/r) B cell non-Hodgkin lymphoma (B-NHL).Primary Objective:To evaluate the safety and tolerability of CB-010 therapy (pluslymphodepletion) in patients with r/r B-NHL subtypes to define themaximum tolerated dose (MTD) and/or recommended dose for expansion(RDE) to determine RP2D.
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 and Immunogenicity of mRNA-4157 Alone or in Combination in Participants with Solid Tumors
This is a 2-part, open-label, Phase 1, multicenter dose-escalation, FIH study of mRNA-4157 monotherapy in subjects with resected solid tumors (Part A) who are in the adjuvant setting (i.e.,status post-resection, including: those who have completed standard of care or have refused standardof care adjuvant therapy) and of mRNA-4157 in combination with pembrolizumab in subjects withunresectable (locally advanced or metastatic) solid tumors (Part B).Part A: an mTPI dose-escalation design will be used. Eligible subjects will each receive a fixed doseof 0.04 mg, 0.13 mg, or 0.39 mg of mRNA-4157 administered via an IM injection on Day 1 of each21-day cycle. Study Day 1 is the day corresponding to the first injection of mRNA-4157 (C1D1).Dosing will be staggered by 1 week between the first and next subject in the first cohort for safetymonitoring purposes. Subjects who do not have a dose limiting toxicity (DLT) following the first 21-day cycle of mRNA-4157 may continue to receive mRNA-4157 on Day 1 of subsequent 21-daycycles, for a maximum of 4 cycles. Intermediate doses may be implemented if determined necessaryby the SRC (Section 3.1.2).After the first 3 subjects have completed the DLT observation period, the safety and tolerability datawill be reviewed by the mRNA-4157 SRC and the decision will be made to dose-escalate, continueenrolling at that dose level (expansion), dose de-escalate, or stop dosing due to unacceptable toxicityon the basis of the dose escalation guidelines described in Section 3.1.2. The rules described inSection 3.1.2 will be used to determine further enrollment at the current dose level. Subjects will beassigned to a dosing cohort based on the order of dose escalation and where cohort slots are open.Part B: The Dose Escalation Phase of Part B will begin after the first dose level from Part A iscleared by the SRC. Thereafter, Parts A and B will run concurrently. An interactive voice responsesystem or similar system will be used to allocate eligible subjects to each cohort in both Part A and Bof the study; note that because the subject population is different for Parts A and B, individualsubjects can only participate in the Part of the study they are eligible for.Dose escalation of mRNA-4157 in Part B will be conducted using the mTPI design in a similarmanner to Part A (with a fixed dose of pembrolizumab for all subjects in Part B).Each subject will receive a maximum of 4 cycles of mRNA-4157, and subjects in Part B maycontinue pembrolizumab until progression, unacceptable toxicity, or up to 35 cycles (2 years oftreatment), whichever is sooner (Section 5.3)After completion of the Part B Escalation Phase, the Part B Expansion Phase may then enroll up to30 additional subjects per dose level, at 1 or 2 doses (as determined by the SRC), at and/or below thecombination RP2D (i.e., a maximum of 60 subjects in the Expansion Phase if 2 dose levels arestudied). If 2 dose levels are studied in the Expansion Phase, subjects will be randomly allocated toeach dose level. Of these Expansion Phase subjects, at least one sub-cohort of 10 subjects may beincluded in order to obtain a mandatory on-treatment tumor biopsy to assess the biological activity ofmRNA-4157 in combination with pembrolizumab in tumors. The first 10 subjects who consent tomandatory on-treatment biopsies will be placed into a biopsy sub-cohort if such a cohort is open(otherwise on-treatment biopsies are optional in the Expansion Phase). If 2 dose levels are studied inthe Part B Expansion Phase, then 2 biopsy sub-cohorts may be included, 1 at each dose level.The same stopping rule as the dose Escalation Phase will also be applied in the Expansion Phase,such that if the rate of AEs meeting DLT criteria at the RP2D (or any lower dose used in theExpansion Phase) is 30% or higher, then recruitment at that dose level will be stopped. A thorough and in-depth review of all the study data would be performed, and the SRC may consider expansionof a lower dose level.There will be no Part A Expansion Phase for subjects in the adjuvant setting.
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)