A Phase 1 First in Human Study of ARV-393 in Adult Participants with Advanced Non-Hodgkin s Lymphoma
This is a multicenter, open-label Phase 1 study testing a new drug called ARV-393 in adults with advanced non-Hodgkin lymphoma (NHL). The study will look at the side effects of the drug, how well it works, and how the body processes it. Initially, the focus will be on ARV-393 by itself. To find the best dose, the study will group patients into sets of three. The goal is to find a dose that causes side effects in about 25% of patients. Doctors will decide whether to increase or decrease the dose based on the side effects and other information. There will be a waiting period of at least 24 hours between giving the first dose to the first patient in a group and the next doses. If the first patient does not have any side effects, more patients can receive that dose. If there are too many side effects, the dose will be lowered. Each dose level will include a small number of patients who will be closely monitored. If the rate of side effects is lower than the target, the dose can be increased; if it is higher than the target, the dose will be lowered. The study will stop if there are serious concerns about the side effects at any dose. When the dose escalation is finished, the best dose will be the one that results in the side effect rate closest to 25%.
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)
A Phase 1 Study of GC012F a Chimeric Antigen Receptor T-cell (CAR T) Therapy Targeting CD19 and B-cell Maturation Antigen (BCMA) in Early-Line Treatment in Subjects with Multiple Myeloma
This is a Phase 1 study testing if the study medicine AZD0120 (Chimeric Antigen Receptor T-cell (CAR T) Therapy) is safe, effective, and has fewer side effects in treating adult patients with Early Line Multiple Myeloma (ELMM). CAR T-cell therapy is a type of treatment that uses patient's own T cells, which are genetically modified to fight his/her cancer. The study team will collect each patient’s T cells, called peripheral blood mononuclear cells (PBMC), to generate AZD0120. Each patient will then receive a medicine called lymphodepletion treatment for 3 days. Following this, after 5-7 days, all patients will receive a single injection of the study medicine AZD0120. All the patients will be divided into two groups. For group 1, the study team will include three patients at a time to receive the study medicine. They will gradually increase the dose of the study medicine for each new group until they find out the dose that is safe and works well for the patients. For group 2, the study team will include more patients to receive the study medicine at a dose that worked well. All patients will have their blood samples taken to see how their body is handling the study treatment and if the study treatment is working well. Special scans will be taken for all patients to see how their cancer is responding to the study treatment. All patients will be closely monitored for safety and any side effects and will be followed for up to 2 years after AZD0120 injection to ensure ongoing safety.
A Phase 1 Study of Lenalidomide in Combination with EPOCH Chemotherapy for HTLV-Associated Adult T-Cell Leukemia-Lymphoma (ATLL)
This study is being done to determine if we can combine lenalidomide with full doses of EPOCH chemotherapy for your ATLL, and to define the highest dose and longest duration of lenalidomide that can be given safely in combination with EPOCH.
A Phase 1 Study of MOMA-313 Given as Monotherapy or in Combination With a PARP Inhibitor in Participants With Advanced or Metastatic Solid Tumors
This is a study testing MOMA-313, a drug that blocks a protein called DNA polymerase theta (Pol?) for prostate cancer with a genetic feature called homologous repair deficiency, most commonly with mutation in the gene BRCA2. The drug is being tested by itself or combined with another drug called olaparib, which blocks a different protein (PARP). There are two groups of patients: one group will get MOMA-313 alone, and the other group will get both MOMA-313 and olaparib. In the first group, doctors will test different doses to find the best amount that is effective and with the least amount of side effects to give patients. If patients do well but don't have a strong response to MOMA-313 alone, they may be switched to get both drugs together. The study will also look at how food ate by a patient affects MOMA-313 and how it interacts with olaparib.
A Phase 1 Study of Nivolumab in Combination with ASTX727 in B-cell lymphoma (NHL or HL) with an Expansion Cohort in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
This study has two parts: first, the study team wants to figure out the amount with few side effects of two drugs, nivolumab and ASTX727, to use together to treat Diffuse Large B-Cell Lymphoma (DLBCL). The study team will start with a small group of patients, see if there are any side effects, and if not, try the same amount with another small group of patients. If too many patients have side effects, the study team will try a lower amount. The goal is to find the best dose where few to no patients have side effects. Once the study team knows the correct dose they are looking for, they will move to the second part of the study, where they will treat a bigger group of patients to see how well the treatment works and if there are any side effects. If too many patients in the larger group have side effects, the study team will stop taking in more patients. After the study, the study team will look at the data to see how often patients had side effects and how well the treatment worked treating DLBCL.
A Phase 1 Study of NKX019 a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy in Subjects with Lupus Nephritis
The purpose of this study is to investigate NKX019, which is made from one type of white blood cell called a natural killer (NK) cell. Those cells are present in healthy subjects and in patients. The NK cells used in NKX019 are taken from the blood of healthy donors. These cells are then modified so that they can identify and remove cells which have a marker on their surface called CD19. CD19 is present on the surface of almost all B cells (another type of immune cell). Studies have shown that by removing these B cells, the harmful antibodies that attack the body’s own tissues in lupus will also be eliminated. This could potentially slow or stop progression of lupus in the body’s organs.