Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors

Purpose
BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials and methods
This was a phase-I (NCT03444753) study that assessed the safet…

Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria

Background
Numerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, par…

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer

Background
SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG4-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion prot…

Cancer vaccines compensate for the insufficient induction of protective tumor-specific immunity of CD3 bispecific antibody therapy

Background
CD3 bispecific antibody (CD3 bsAb) therapy has become an established treatment modality for some cancer types and exploits endogenous T cells irrespective of their specificity. However, durable clinical responses are hampered by immune esca…

HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAFV600E-mutant microsatellite stable colorectal cancer

Background
B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E-mutant microsatellite stable (MSS) colorectal cancer (CRC) constitutes a distinct CRC subgroup, traditionally perceived as minimally responsive to standard therapies. Recent clinical…

Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment

Background
Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that …

Durvalumab and tremelimumab in combination with metronomic oral vinorelbine for recurrent advanced cervical cancer: an open-label phase I/II study

Background
The MOVIE phase I/II trial (NCT03518606) evaluated the safety and antitumor activity of durvalumab and tremelimumab combined with metronomic oral vinorelbine in patients with advanced tumors. We present the results of the recurrent advanced…

Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study

Background
Second-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoi…

Targeted inhibition of Aurora kinase A promotes immune checkpoint inhibition efficacy in human papillomavirus-driven cancers

Background
Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inh…

Early treatment discontinuation in patients with deficient mismatch repair or microsatellite instability high metastatic colorectal cancer receiving immune checkpoint inhibitors

Background
Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 yea…

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