P1, N=42, Recruiting, Genmab | N=30 --> 42 | Trial primary completion date: Jul 2026 --> Mar 2026

Due to the unique epitope, it demonstrates superior activation compared to APX005M (S267E)...Furthermore, in humanized transgenic mice challenged with huPD-L1-expressing tumor cells, BA4415 induced superior anti-tumor activity. This novel anti-PD-L1/CD40 bispecific antibody holds potential for strong anti-tumor therapeutic efficacy by selectively restricting CD40 stimulation in tumors.

P1, N=163, Active, not recruiting, AbbVie | Trial completion date: Mar 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025

P1, N=18, Recruiting, University of Southern California | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

P1, N=30, Not yet recruiting, Akamis Bio | Initiation date: Nov 2024 --> Feb 2025

P1/2, N=88, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting

These findings suggest that CD40 agonists are promising immunotherapeutic candidates for pediatric B-ALL, warranting further clinical investigations to improve patient outcomes in CD40-expressing B-ALL.

In both virus-induced and neoantigen-based mouse tumor models, BiA9*2_HF demonstrates therapeutic efficacy and elevated safety profile, with complete tumor clearance, as well as measured abscopal impact on tumor growth. The BiA9*2_HF drug candidate can thus be utilized to tailor immunotherapeutics for cancer patients.

P1, N=126, Active, not recruiting, Lyvgen Biopharma Holdings Limited | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025

P1, N=1, Active, not recruiting, Providence Health & Services | Enrolling by invitation --> Active, not recruiting | N=24 --> 1

This phase 1a study provided initial proof-of-mechanism for NG-350A, with strong evidence of tumor delivery, viral replication and transgene expression-particularly after intravenous dosing. The lack of transgene-related or off-target viral toxicity was consistent with the highly selective delivery and replication of NG-350A, even after systemic delivery. The efficacy of intravenous-dosed NG-350A will now be evaluated in combination with pembrolizumab (NCT05165433), as well as with chemoradiotherapy (NCT06459869).

Finally, a toxicology study in cynomolgus monkeys demonstrated that KHK2840 activated the CD40 signal with tolerable toxicological properties. These results indicate that KHK2840 is a novel and potent hCD40 agonistic antibody for cancer immunotherapy, which is expected to augment the antitumor efficacy of ICIs and chemotherapy.

These encouraging results from OPTIMIZE-1 form the basis of a future randomized confirmatory trial of mitazalimab in combination with mFOLFIRINOX in mPDAC. Ethics Approval The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines as defined by the International Conference on Harmonisation, in 14 European University Hospitals according to the study protocol and amendments, approved by local Institutional Review Boards and independent ethics committees: France:Comité de protection des personnes Est I, Centre hospitalier la Chartreuse - 1 Bld Chanoine Kir, BP 23314 21033 DIJON France Belgium: CHU UCL Namur, site Godinne, Comité d'éthique, Avenue Docteur G. Thérasse 1, 5530 YVOIR Spain: The CEIm of the Ramón y Cajal University Hospital, Madrid, Spain Patients provided written informed consent before enrolment.Download figure Open in new tab Download powerpoint Abstract 592 Figure 1 OPTIMIZE-1 dosing regimen and biomarker planView this table:View inline View popup Download powerpoint Abstract 592 Table 1 OPTIMIZE-1 outcomes

P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Trial completion date: Apr 2025 --> Nov 2024

P1, N=160, Active, not recruiting, Shattuck Labs, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Apr 2025 --> Nov 2024

P1/2, N=40, Terminated, AbbVie | Completed --> Terminated; Strategic considerations

MEDI5083 maximum tolerated dose was 5 mg. Objective response rate was 2.8% (1 partial response and 11 stable disease). MEDI5083 toxicity profile limits its further development.

P1, N=30, Recruiting, Genmab | Trial completion date: Oct 2027 --> Feb 2027

P1, N=150, Active, not recruiting, AbbVie | Trial completion date: Sep 2024 --> Mar 2025 | Trial primary completion date: Sep 2024 --> Mar 2025

P1, N=198, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1

P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Trial primary completion date: Jul 2024 --> Dec 2024

P1, N=20, Recruiting, University of Pennsylvania | Not yet recruiting --> Recruiting

P1, N=196, Recruiting, Chipscreen Biosciences, Ltd. | Not yet recruiting --> Recruiting | Initiation date: Oct 2023 --> Jan 2024

P1/2, N=22, Completed, Craig L Slingluff, Jr | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Mar 2024 | Trial primary completion date: Sep 2024 --> Mar 2024

P2, N=54, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P1/2, N=94, Active, not recruiting, Alligator Bioscience AB | Recruiting --> Active, not recruiting

P1, N=42, Completed, Yale University | Active, not recruiting --> Completed | Trial completion date: Oct 2027 --> May 2024

To overcome these issues, in this study, we have developed a multifunctional Immunosome where αCD40 is conjugated on the surface and RRX-001, a small molecule immunomodulator was encapsulated inside it...In addition, Immunosomes treated long-term surviving mice showed tumor specific immune memory response which prevented tumor growth upon rechallenge. Our results suggested that this novel formulation can be further explored in clinics to improve in vivo anti-tumor efficacy of αCD40 with long-lasting tumor specific immunity while reducing the associated toxicities.

P1, N=18, Recruiting, University of California, San Diego | Not yet recruiting --> Recruiting

P1, N=26, Active, not recruiting, Yale University | Recruiting --> Active, not recruiting

P1, N=163, Active, not recruiting, AbbVie | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

In a humanized mouse model for CD40 and FcγRs, 2141-V11 induced TLS formation in mice bearing orthotopic breast carcinoma, correlating with local and abscopal antitumor effects, systemic immune activation, and immune memory. These findings support the safety and efficacy of 2141-V11, warranting phase 2 studies and suggesting a unique mechanism of action for this Fc-enhanced immunotherapy (NCT04059588).

P1, N=30, Not yet recruiting, Akamis Bio

P1; N=45 --> 30

P1/2, N=46, Not yet recruiting, Darell Bigner

Mitazalimab with mFOLFIRINOX demonstrated manageable safety and encouraging activity, warranting continued development in a phase 3, randomised, controlled trial. The results from OPTIMIZE-1 pave the way for further exploration and confirmation of a novel immunotherapy treatment regimen for metastatic pancreatic ductal adenocarcinoma, which is a complex and aggressive cancer with very low survival rates and restricted treatment options.

Furthermore, the abundance of Faecalibaculum, one of the probiotics critical for tumor suppression, was obviously increased in the combination of 5C11 and β-glucan-treated mice. These data reveal a novel mechanism of tumor suppression upon the combination treatment of 5C11 and β-glucan and propose that the combination treatment of agonistic anti-human CD40 antibody 5C11 and β-glucan could be a promising therapeutic strategy for cancer patients.

P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Enrolling by invitation --> Active, not recruiting

The technology was applied to an effector function enhanced agonist CD40 antibody, SEA-CD40, and experiments demonstrate significant reductions in Fc-induced immune activation in vitro and in mice and nonhuman primates despite showing retained efficacy and improved pharmacokinetics compared to the parent antibody. We foresee that this simple, modular system can be rapidly applied to antibodies that suffer from systemic immune activation due to peripheral FcγR binding immediately upon infusion.

Enhancing efficacy is the most important driver for this development, and approaches that maximize the ability of CD40 to both remodel the tumor microenvironment and boost the anti-tumor T cell response provide great opportunities to benefit cancer patients. Enhanced understanding of the role of different CD40 expressing immune cells in the tumor microenvironment may facilitate more efficient clinical development of these compounds.

P1, N=18, Not yet recruiting, University of California, San Diego | Initiation date: Feb 2024 --> Jun 2024

P1, N=150, Active, not recruiting, AbbVie | Trial completion date: Nov 2023 --> Sep 2024 | Trial primary completion date: Nov 2023 --> Sep 2024