Treatment Of Refractory Cancer Patients Research Articles

Abstract CT136: Interim safety and efficacy results from a phase 1b study of CM24 in combination with nivolumab in adults with advanced solid tumors

Abstract Objectives: The monoclonal antibody CM24 binds to and blocks carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), which is known to have several important roles in cancer progression. A Phase 1/2 study (NCT 04731467) includes in its Phase 1 part, a dose escalation of CM24 administered with nivolumab for the treatment of refractory cancer patients. The primary objectives of this part are to evaluate safety, tolerability, PK and determine the recommended Phase 2 dose (RP2D) of CM24. In the Phase 2 part of this study, patients with NSCLC relapsed from or refractory to first-line immuno-oncology will be treated with CM24 and nivolumab, and patients with advanced/metastatic pancreatic adenocarcinoma relapsed from or refractory to first-line therapy will be treated with CM24, nivolumab, and chemotherapy, the objective will be to evaluate safety and preliminary efficacy of the combination treatment. Methods: In the dose escalation part of the study, enrolled patients were administered with CM24 at 10, 15 and 20mg/kg q2w and nivolumab 480mg q4w. Safety was assessed according to CTCAE v5 and preliminary anti-tumor activity was assessed by the investigators according to RECISTv1.1 using CT/MRI. CM24 and CEACAM1 measurements in serum, biopsy specimens and TILs, as well as tumor and TILs PD-L1 levels were determined. Results: As of data cutoff date of January 31, 2022, a total of 13 patients were in the dose escalation phase, of which 10 are evaluable for dose limiting toxicity (DLT) determination, including 7 with pancreatic cancer (PDAC), 2 with colorectal cancer (CRC) and one with papillary thyroid cancer (PTC). All patients but one had received 2 prior regimens for metastatic disease. Six Grade 3 adverse events (AEs) (unrelated to CM24 or nivolumab), were observed, each in a single patient, including diarrhea, hypokalemia, abdominal pain, small bowel obstruction, atrial flutter, and GI bleed. No Grade 4 AEs or deaths were reported. For the 10 evaluable patients, best overall response included one confirmed PR (PDAC patient, 6-month duration of response) two SD (one PDAC and one PTC patient, both with duration of 3.5 months), and two patients are awaiting follow up MRI/CT scans. As of the cutoff date, 8/10 of the patients that completed the DLT period are on treatment or in follow up (range 2 to 9.5 months). Pharmacokinetic analysis of CM24 shows exposure is dose-related and approximately dose-proportional. Dose proportionality is shown by CLss and dose normalized Cmax and AUC. Receptor occupancy analyses in peripheral blood reached a mean of 100% occupancy of CEACAM1 by CM24 at the higher dose levels. Conclusion: The Phase 2 portions of the study will be initiated at the conclusion of this dose escalation part. Citation Format: Erkut Borazanci, Mohammed Najeeb Al Hallak, Joseph P. Eder, Talia Golan, Shubham Pant, Ruth Perets, Gal Markel, Michael Schickler, Hadas Reuveni, Lixian Jin, Bertrand Liang, Alexander I Spira. Interim safety and efficacy results from a phase 1b study of CM24 in combination with nivolumab in adults with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT136.

77. Serial Treatment of Refractory Cancer Patients with GM-CSF Expressing Oncolytic Adenovirus Enhances Immunological Response and Survival without Compromising Safety

77. Serial Treatment of Refractory Cancer Patients with GM-CSF Expressing Oncolytic Adenovirus Enhances Immunological Response and Survival without Compromising Safety

Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

ObjectivesCholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated.MethodsEighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections.ResultsLDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1β and tumor necrosis factor-α), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase IIα and tubulin).ConclusionThe ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.

177. Treatment of Refractory Cancer Patients with a Serotype 5/3 Chimeric Oncolytic Adenovirus Expressing Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF): Virological, Immunological and Clinical Endpoints

177. Treatment of Refractory Cancer Patients with a Serotype 5/3 Chimeric Oncolytic Adenovirus Expressing Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF): Virological, Immunological and Clinical Endpoints