Advanced Malignant Solid Neoplasm Clinical Trial
Official title:
Pilot Study of DS-8201a Pharmacodynamics in Patients With HER2-Expressing Advanced Solid Tumors
This phase I trial studies the biological effects of DS-8201a on patients with HER2 positive cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). DS-8201a works by binding to a protein called HER2 that is present on the surface of tumor cells. This allows DS-8201a to kill the tumor cells by damaging their deoxyribonucleic acid (DNA), resulting in tumor cell death. This study looks at how DS-8201a may affect the levels of certain proteins and immune cells in tumors and how well the drug works against tumor cells by examining cells from a small piece tumor taken before and after DS-8201a is given.
PRIMARY OBJECTIVE: I. To assess the effects of trastuzumab deruxtecan (DS-8201a) on total Top1 levels in biopsy specimens from patients with HER2-expressing advanced solid tumors, at early and late post-treatment time points, thereby establishing the degree and duration of DS-8201 target engagement. SECONDARY OBJECTIVES: I. To assess any associations between serum concentrations of DS-8201a and the effects of DS-8201a on total Top1 levels in tumor biopsy specimens. II. To determine the safety and tolerability of DS-8201a administered intravenously every 3 weeks, in 21-day cycles, at a dose of 5.4 mg/kg. III. To determine the overall response rate (complete response [CR] + partial response [PR]) for patients administered intravenously with DS-8201a every 3 weeks, in 21-day cycles, at a dose of 5.4 mg/kg. EXPLORATORY OBJECTIVES: I. To evaluate the effects of DS-8201a on CD8+ T cell infiltration and activation in tumor, tumor PD-L1 and HER2 expression, and DDR signaling (for example: gamma H2AX, RAD51, and phosphorylated [p]NBS1) in biopsy specimens. II. To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with DS-8201a response or resistance. III. To examine any associations between baseline tumor HER2 amplification or HER2 expression level and response to DS-8201a. IV. To evaluate the effects of DS-8201a on tumor levels of HER2 and DDR-associated proteins. V. To examine any tumor genomic alterations that may be associated with resistance to DS-8201a. VI. To evaluate anti-drug antibodies following administration of DS-8201a. OUTLINE: Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), computed tomography (CT) or magnetic resonance imaging (MRI), biopsies, and collection of blood samples throughout the study. After completion of study treatment, patients are followed up for 40 days. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05039801 -
IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors
|
Phase 1 | |
| Completed |
NCT02317874 -
Testing the Addition of the Anti-Cancer Drug Talazoparib to the Combination of Carboplatin and Paclitaxel for the Treatment of Advanced Cancer
|
Phase 1 | |
| Recruiting |
NCT05691491 -
Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT03218826 -
PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery
|
Phase 1 | |
| Withdrawn |
NCT03925428 -
Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas
|
Phase 1 | |
| Active, not recruiting |
NCT03233204 -
Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Active, not recruiting |
NCT02389309 -
Dasatinib, Temsirolimus, and Cyclophosphamide in Treating Patients With Advanced, Recurrent, or Refractory Solid Tumors
|
Phase 1 | |
| Active, not recruiting |
NCT03065387 -
Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
|
Phase 1 | |
| Terminated |
NCT04552704 -
CD24Fc for the Treatment of Immune Related Adverse Events in Patients With Advanced Solid Tumors, TIRAEC Study
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT03213691 -
Selumetinib Sulfate in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Recruiting |
NCT02408861 -
Nivolumab and Ipilimumab in Treating Patients With HIV Associated Relapsed or Refractory Classical Hodgkin Lymphoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
|
Phase 1 | |
| Recruiting |
NCT05638295 -
Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)
|
Phase 2 | |
| Recruiting |
NCT05455606 -
Does the Use of a Genomic Tumor Board Increase the Number of Patients Who Receive Genome-Informed Treatment
|
N/A | |
| Recruiting |
NCT05101356 -
A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT03220035 -
Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Completed |
NCT02451553 -
Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer
|
Phase 1 | |
| Active, not recruiting |
NCT03213678 -
Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Active, not recruiting |
NCT01480154 -
Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer
|
Phase 1 | |
| Active, not recruiting |
NCT04514484 -
Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV
|
Phase 1 | |
| Active, not recruiting |
NCT03842228 -
Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations
|
Phase 1 |