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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
A number of examples of PD-1-targeted antibodies are described below. Nivolumab (Opdivo™), pembrolizumab (KeytrudaTM), and cemiplimab (LibtayoTM) are approved by the FDA and many other other Western countries, while toripalimab (TuoyiTM), tislelizumab, sintilimab (Tyvyt™), and camrelizumab have been approved (conditionally in some cases at the time of writing) by the Chinese FDA. Several other PD-1-targeted antibodies are at various stages of clinical development for a wide range of hematological and solid tumor indications but are not discussed any further here. These include spartalizumab (PDR001; Novartis), dostarlimab (TSR-042, WBP-285; GlaxoSmithKline), retifanlimab (INCMGA00012, MGA012; Incyte and MacroGenics), AMP-224 (AstraZeneca/MedImmune and GlaxoSmithKline), and AMP-514 (MEDI0680; AstraZeneca).
Uterine Malignancies
Published in Malte Renz, Elisabeth J. Diver, Whitfield B. Growdon, Oliver Dorigo, Synopsis of Key Gynecologic Oncology Trials, 2019
Malte Renz, Elisabeth J. Diver, Whitfield B. Growdon, Oliver Dorigo
Study: GARNET, NCT02715284, ongoing Citation: Abstract presented at ESMO 2018 (Oaknin, Leath et al. 2018)Highlight: TSR-042, humanized monoclonal PD-1 antibody = dostarlimabDesign: Ongoing phase I trial: Patients with advanced or recurrent pretreated microsatellite instability-high (MSI-H) endometrial cancerTreated with anti-PD-L1 monoclonal antibody, TSR-042, 500 mg q 3 weeks for first 4 cycles and 1000 mg q 6 weeks thereafterResults: 17 patients with at least one tumor assessmentPR: 9/17 (53%)SD: 1/17 (6%)PD: 6/17 (35%)≥Grade 3 AE in one patient (leukopenia)Conclusion: → Robust clinical activity and acceptable toxicity
Experimental drugs for fallopian cancer: promising agents in the clinical trials and key stumbling blocks for researchers
Published in Expert Opinion on Investigational Drugs, 2022
Raffaella Cioffi, Federica Galli, Emanuela Rabaiotti, Massimo Candiani, Francesca Pella, Giorgio Candotti, Luca Bocciolone, Patrizia De Marzi, Giorgia Mangili, Alice Bergamini
Dostarlimab is an anti-PD1 antibody currently being tested in combination therapies in phase II/III trials for first-line and recurrent disease. Preliminary results from a phase II trial based on the combination of dostarlimab, bevacizumab, and niraparib, which enrolled 41 platinum-resistant patients, have been reported in a recent abstract: the ORR was 17.9%. Median PFS was 7.6 months [55]. MITO33 (NCT04679064) (NItCHE) is a phase III ongoing trial, evaluating the efficacy of the combination of dostarlimab and niraparib versus investigator’s choice monochemotherapy in relapsed ovarian cancers that were not candidates for platinum retreatment [56]. Dostarlimab activity is currently being investigated in the first-line setting in FIRST trial, a phase III comparing dostarlimab plus niraparib in combination with paclitaxel and carboplatin in stage III/IV tumors (NCT03602859) [57].
Immune checkpoint inhibitors for recurrent endometrial cancer
Published in Expert Review of Anticancer Therapy, 2022
Levent Mutlu, Justin Harold, Joan Tymon-Rosario, Alessandro D. Santin
Dostarlimab is a humanized anti-PD-1 monoclonal antibody. The Phase I GARNET trial [40] investigated dostarlimab in recurrent endometrial cancer that progressed after prior platinum-based chemotherapy. Analysis of the 71 patients with MMRd uterine cancer demonstrated an observed response rate of 42.3%; 9 patients (12.7%) had a complete response, and 21 patients (29.6%) had a partial response. The median PFS was 8.1 months, while the median overall survival was not reached. The most frequent treatments related to adverse events were asthenia, diarrhea, and fatigue. Grade 3 or higher adverse events were 11.5%, and anemia was the most common side effect. The results from the expansion phase of the trial showed an ORR 44.7% in the MMR deficient arm, as opposed to a 13.7% ORR in the MMR proficient/MSS arm. [41] Based on the results of the GARNET trial, FDA granted accelerated approval for dostarlimab in MMRd advanced or recurrent endometrial cancer. Dostarlimab is currently under investigation in a Phase III trial (Ruby, NCT03981796) in combination with carboplatin/paclitaxel in recurrent or primary advanced endometrial carcinoma.
Antibodies to watch in 2020
Published in mAbs, 2020
Hélène Kaplon, Mrinalini Muralidharan, Zita Schneider, Janice M. Reichert
Described by GlaxoSmithKline as Phase 1/2,97 the GARNET study evaluated the safety and efficacy of dostarlimab as a monotherapy for patients with advanced solid tumors, including women with recurrent or advanced endometrial cancer who progressed on or after a platinum-based regimen. Patients were administered dostarlimab 500 mg once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression. Data from 125 patients, including 41 MSI-H (33%), and 79 MSS (63%) patients, as well as 5 with an unknown MSI-status (4%), were analyzed. Preliminary results showed that the overall response rate in the full population, MSI-H population, and MSS population were 30%, 49%, and 20%, respectively, while the disease control rate in these populations were 53%, 63% and 47%, respectively. In general, adverse events were Grade 1 or 2, with only 13.6% of patients experiencing Grade 3 or higher adverse events.97