A Phase 1b Study of Nivolumab in Patients with Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)
Nivolumab will be investigated at the Food and Drug Administration (FDA)-approved dose of480 mg intravenous (IV) every 4 weeks until unacceptable toxicity, disease progression, orcompletion of 2 years of therapy. If that dose and schedule have unacceptable toxicity, thenenrollment will cease for that particular disorder/severity group. Depending on accumulatedexperience from this study and other emerging literature, additional doses and schedules may beconsidered.This study is designed to enroll cohorts of up to 12 patients for each disease cohort who will betreated with nivolumab at the standard dose at each disease severity level. For each autoimmunedisorder, patients with different severity of the disease, as defined by disease-specific severityindices, will be assessed.Patients will initially be enrolled into the mild and moderate cohorts (exact designations in Table1). If nivolumab is well tolerated in this study population, then enrollment to more severecohorts will be opened following discussions with Cancer Therapy Evaluation Program(CTEP)/National Cancer Institute (NCI) and study teams at participating sites.
A Phase 1b Study to Evaluate the Safety Tolerability and Preliminary Efficacy of ATP150/ATP152 VSV-GP154 and Ezabenlimab (BI 754091) in Patients with KRAS G12D/G12V Mutated Pancreatic Ductal Adenocarcinoma
This is an open-label, phase 1b study comprising two parts (safety and immunogenicity part and randomized efficacy part) to evaluate the safety, tolerability, preliminary efficacy, and immunogenicity of a heterologous prime-boost vaccine (protein and viral vector) strategy, in which approximately 90 patients with resected KRAS G12D/G12V mutated pancreatic cancer and colorectal cancer after (neo-) adjuvant chemotherapy or chemoradiotherapy will be enrolled in the following treatment parts of the study:Part 1 (Safety and Immunogenicity Part) – PDAC and CRC patientsPart 2 (Efficacy Part) – PDAC patients only
A Phase 1b Trial of ZEN003694 (ZEN-3694) with Pembrolizumab and Nab-Paclitaxel in Patients with Metastatic Triple-Negative Breast Cancer
This is a phase 1b study testing whether the study medicine ZEN003694 (BET bromodomain inhibitor), together with pembrolizumab (immunotherapy) and nab-paclitaxel (standard chemotherapy), works well and has fewer side effects as treatment for patients with triple-negative breast cancer that has spread to other parts of the body (advanced). This study has two parts. In Part 1, patients will receive the study medicine along with pembrolizumab and nab-paclitaxel. The study team will gradually increase the dose of the study medicine to find out the dose that works well and has fewer side effects. In Part 2, more patients will be added to receive ZEN003694 alone for the first seven days, followed by the combination of medicines, including ZEN003694, pembrolizumab, and nab-paclitaxel, at the dose found to be effective and safe in part 1 of the study. The study team will have blood samples taken from all patients to see how their bodies are handling the study medicine. All patients will have special scans done to see how the medicine is changing their cancer. Tumor tissue samples will be collected from all patients to learn more about their cancers. All patients will be closely monitored for potential side effects and safety concerns.
A PHASE 1B/2 MULTICENTER OPEN-LABEL STUDY OF IFINATAMAB DERUXTECAN (I-DXd) A B7-H3 ANTIBODY-DRUG CONJUGATE (ADC) IN COMBINATION WITH ATEZOLIZUMAB WITH OR WITHOUT CARBOPLATIN AS FIRST-LINE INDUCTION OR MAINTENANCE IN SUBJECTS WITH EXTENSIVE-STAGE SMALL CELL LUNG CANCER (ES-SCLC) (IDeate-Lung03)
This global study is designed to test how safe and effective the drug I-DXd is when combined with atezolizumab, with or without carboplatin. The treatment will be used either as ongoing maintenance therapy or as part of a short initial treatment followed by maintenance. The study will take place at multiple locations in the United States, Europe, and Japan. It has two main parts: Part A focuses on checking safety, while Part B adjusts the doses to find the best amount to use. Patients must be able to perform normal daily activities and can join even if they have brain metastases that don’t cause symptoms. A type of radiation therapy called prophylactic cranial irradiation (PCI) is allowed if the patient’s cancer responds well to the treatment. The study will start by testing one group to see if thedoses are safe before adding more groups and eventually randomizing patients. Previous studies suggest that combining I-DXd and atezolizumab should have manageable side effects. Researchers may add new treatment options to the study later if needed.
A Phase 1b/2 Open-label Umbrella Study to Evaluate Safety and Efficacy of Elacestrant in Various Combinations in Patients with Metastatic Breast Cancer (ELEVATE)
This is a multicenter, Phase 1b/2 trial. The Phase 1b part of the trial aims to determine the RP2D of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, and ribociclib. The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations in patients with ER+/HER2- advanced/metastatic breast cancer.
A PHASE 1B/2 PAN-TUMOR OPEN-LABEL STUDY TO EVALUATE THE EFFICACY AND SAFETY OF IFINATAMAB DERUXTECAN (I-DXD) IN SUBJECTS WITH RECURRENT OR METASTATIC SOLID TUMORS (IDeate-Pantumor02)
This is a global, multicenter, pan-tumor, open-label, single-treatment arm, parallel-cohort, Phase 1b/2 study ofI-DXd in subjects with recurrent or metastatic solid tumors previously treated with 1 or more systemic therapiesfor the selected tumor indication.This study will consist of 13 cohorts targeting the following tumor types: endometrial cancer (EC); head and necksquamous cell carcinoma (HNSCC); pancreatic ductal adenocarcinoma (PDAC); colorectal cancer (CRC);hepatocellular carcinoma (HCC); adenocarcinoma of esophagus, gastroesophageal junction, and stomach(Ad-Eso/GEJ/gastric); urothelial carcinoma (UC); ovarian cancer (OVC); cervical cancer (CC); biliary tractcancer (BTC); human epidermal growth factor 2 (HER2)-low breast cancer (BC); HER2 immunohistochemistry(IHC) 0 BC; and cutaneous melanoma.Each cohort starts with Stage 1 and may continue to Stage 2 if sufficient safety and efficacy data are observed.Throughout both stages, subjects will be closely monitored for safety.
A Phase 1b/2 Study of AZD0120 (also known as GC012F) a Chimeric Antigen Receptor T Cell Therapy Targeting CD19 and B cell Maturation Antigen in Participants with Relapsed or Refractory AL Amyloidosis
Open-label Phase 1b/2 study with primary objective of this study is to evaluate the safety, tolerability and efficacy of AZD0120 in participants with light chain (AL) amyloidosis.
A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants with RCC (KEYMAKER-U03): Substudy 03C in Participants With Recurrent Disease During or After Anti-PD-(L)1 Adjuvant Therapy
Despite clear advances that have been taking place in the treatment of advanced RCC in recent years, there are still unmet medical needs and opportunities to improve the overall outcome of patients with kidney cancer. The umbrella platform study design provides the framework for testing investigational agents in substudies of patients who are in need of new treatment options due to an evolving treatment paradigm. The adaptive design of this umbrella study will allow rapid and concurrent evaluation of multiple investigational agents in an efficient manner. This substudy will include participants with advanced ccRCC who have experienced disease recurrence during or after adjuvant treatment with PD-(L)1 inhibitors.
A Phase 1b/2 Study to Demonstrate the Safety and Efficacy of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Subjects With an Ileal Pouch-Anal Anastomosis
The aim of this study is to assess the safety and preliminary efficacy of treatment with EXE-346, a live biotherapeutic product (LBP)containing a fixed proportion mixture of 8 individual bacterial strains, which may reduce bowel movement frequency in patients with an IPAA and lead to a higher quality of life (QoL). The Phase 1b part of the study is an open label (OL), single-arm study to assess the safety of EXE-346 administered orally at a dose of 1500 × 109 CFU BID for up to 4 weeks. The Phase 2 part of the study will initially be a randomized, double-blinded study to assess the safety and efficacy of the same dose of EXE-346 administered orally BID for up to 8 weeks, compared with placebo. Subjects who complete this Phase 2 double-blinded part of the study will be eligible to participate in an optional OL extension phase. Subjects who participate in the optional OL extension phase will receive EXE-346 orally at a dose of 1500 × 109 CFU BID for up to 8 weeks.
A Phase 1b/2a Study of Gemcitabine and Nab-paclitaxel in Combination with VS-6766 and Defactinib in Patients with Previously Untreated Metastatic Adenocarcinoma of the Pancreas
This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with Pancreatic Ductal Adenocarcinoma (PDAC) who have been previously untreated.