CLINICAL
Agenus advancing next-gen CTLA-4 antibody in immunologically cold tumors
Updated Phase 1 data from Agenus at SITC show the company's Fc-enhanced anti-CTLA-4 antibody AGEN1181 induced 17 objective responses across 116 patients representing nine cancer types, including poorly immunogenic microsatellite stable cancers and cancers in individuals who express a low-affinity variant of FCγR3, which have been poorly served by first-generation CTLA-4 inhibitors. An abstract published Nov. 9 reported 13 objective responses across 102 patients. Based on the data, Agenus plans to test AGEN1181 as a monotherapy and with its anti-PD-1 mAbbalstilimab in Phase II/III studies of MSS colorectal cancer, MSS endometrial cancer and ovarian cancer. In October, the company withdrew a BLA seeking accelerated approval for its balstilimab as monotherapy in second-line cervical cancer after FDA granted full approval in the indication to Keytruda pembrolizumab from Merck & Co.
Immutep’s data for LAG3 checkpoint target raise survival questions
The latest data from Immutep at SITC are raising questions about survival benefits of one of the most advanced LAG3 therapies in the pipeline. Those concerns shouldn’t read through to other LAG3 programs because Immutep is targeting a different function of the receptor than competitors, and they may be addressed by narrowing the patient population. The company reported that eftilagimod alpha, a LAG3 fusion protein, plus chemotherapy missed the overall survival endpoint in the Phase 2b AIPAC study. It led to a non-significant 2.9 month increase in overall survival in hormone receptor-positive, HER2-negative metastatic breast cancer patients over placebo plus chemotherapy. In the 227-patient trial, the eftilagimod group had a median OS of 20.4 months compared with 17.5 months for the comparator group (HR=0.88; p=0.197). However, the company reported significant OS increases in three predefined subgroups and noted that AIPAC is one of the first trials to report efficacy after introduction of CDK4/6 inhibitors in prior treatment lines. Patients under 65 years of age had a median OS of 22.3 months compared with 14.8 months in the comparator arm, for a 7.5 month benefit (HR=0.66). In patients with a low monocyte count at the start of the study, median OS was 32.5 months vs. 12.9 months (HR=0.44); and in patients with the aggressive luminal B subtype, median OS was 16.8 months vs. 12.6 months in the comparator arm (HR=0.67). The data from the low monocyte subset support eftilagimod’s mechanism of action as an antigen-presenting cell activator. The fusion protein, which combines a soluble form of LAG3 with IgG1, acts as a MHCII agonist that decouples LAG3’s T cell suppressive checkpoint function from its dendritic cell stimulatory effect, promoting the latter.
PDUFA date around April 2022 for Shanghai Junshi’storipalimab
FDA granted priority review and assigned a PDUFA date on or around April 2022 for toripalimab from Shanghai Junshi Biosciences to treat advanced recurrent or metastatic nasopharyngeal carcinoma in combination with gemcitabine and cisplatin, and as second line or above monotherapy after platinum-containing chemotherapy. The anti-PD-1 antibody is approved in China for melanoma, nasopharyngeal cancer, and urothelial carcinoma. CoherusBioSciences in-licensed rights to develop and commercialize toripalimab in the U.S. and Canada.
Highlight Therapeutics’ BO-112 boosts checkpoint response rate in Phase 2
Highlight Therapeutics has unveiled preliminary results from a Phase 2b study, which combines its double-strand RNA lead candidate, BO-112, with anti-PD-1 treatment in melanoma patients whose disease has progressed on previous anti-PD-1 treatment. Described by the company as activator of dsRNA sensors including RIG-1, MDA5 and TLR3, BO-112 produces a cascade along several pathways, boosting dendritic cells and leading to the expression of PD-L1 that makes tumors visible to the immune system.
