The AACR annual meeting starts tomorrow, where many interesting early-phase immune checkpoint targeted therapies that will be reported on. Here are DRG’s pick of the most interesting novel checkpoint agents featured at the conference.

4-1BB agonists
An FAP-targeted 4-1BB agonist (Roche) has indicated no hepatotoxicity compared to other 4-1BB agonists in pre-clinical trials. The agent’s antitumor efficacy as a monotherapy and combination therapy is encouraging.

(Session PO.IM02.02 - BITES Bispecifics and Checkpoints, 3634/7)

PRS-343 (Pieris Pharmaceuticals) is a 4-1BB/HER2 bispecific antibody. Ex-vivo studies showed HER2-dependent dual anti-tumor responses and formed the basis of an ongoing Phase I study.

(Session PO.IM02.07 - Dendritic Cells as Critical Immune Targets, 3673/16)

Agents in combination with PD-1 /PD-L1 inhibitors

AGEN1884 (Agenus Inc.) in combination with an anti-PD-1 displayed encouraging T-cell responses in vitro.

(Session PO.IM02.02 - Checkpoints 1, 3654/27)

MEDI9197 (MedImmune). Data from in vitro studies in the myeloid and lymphoid immune compartments established the anti-tumor activity of this agent, a TLR7/8 agonist, specifically in combination with PD-1/PD-L1 inhibitors. A Phase I clinical study is ongoing in advanced tumors (NCT02556463).

(Session PO.CL06.01 - Immunomodulatory Agents and Therapeutics, 4697/13)

Immune checkpoint inhibitors in hematological malignancies

Duvortuxizumab (Janssen Biotech). In preclinical lymphoma models duvortuxizumab, an anti-CD3/CD19 monoclonal-antibody (DART), in combination with bendamustine has elicited T-cell mediated anti-tumour activity, with evidence of complete response rates and no relapse.

(Session PO.IM02.05 - BITES Bispecifics and Checkpoints, 3636/9)

MT-3724 (Molecular Templates/ELI Lilly), a CD-20 targeted immunotoxin, has indicated a survival advantage and reduction in tumor size in a preclinical study in ibrutinib resistant mantle cell lymphoma murine cell lines.

(Session PO.IM02.05 - BITES Bispecifics and Checkpoints, 3651/24)

Other notable agents

COM701 (Compugen Ltd.), a PVRIG (B7/CD28) inhibitor, demonstrated reproducible improvement of T cell activation, indicating generation of anti-tumor immune responses in in vitro mice models.

(Session PO.IM02.02 - Checkpoints 1, 581/15)

INCAGN1876 (Agenus Inc./Incyte), a GITR antagonist, has been shown in preclinical studies to enhance T Cell responsiveness to weakly immunogenic tumor antigens, overcoming the suppressive activity of regulatory T cells both as a monotherapy and in combination with other immune checkpoint inhibitors. Phase I/II studies ongoing in advanced tumors (NCT02697591).

(Session PO.IM02.05 - BITES Bispecifics and Checkpoints, 3643/16)

INCAGN1949 (Agenus Inc./Incyte), an OX40 antagonist has shown an optimal agonist profile, linear PK profile and tolerability in preclinical studies. A Phase I/II study ongoing in advanced tumors (NCT02923349).

(Session PO.CL06.01 - Immunomodulatory Agents and Therapeutics, 4703/19)

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