P1, N=184, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.

P1, N=14, Terminated, Nicholas Butowski | Active, not recruiting --> Terminated; Industry sponsor decision

P1/2, N=31, Terminated, Genmab | N=103 --> 31 | Trial completion date: Dec 2026 --> May 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> May 2024; Due to strategic evaluation of GEN1053 within the context of Genmab's portfolio

P1/2, N=103, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting | Trial completion date: Jul 2027 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Sep 2026

Pts received boserolimab 30 mg IV Q6W plus pembro 400 mg IV Q6W for 18 cycles plus nab-paclitaxel 100 mg/m2 (3 weeks on [days 1, 8, and 15]/1 week off). In pts with TNBC and tumors expressing PD-L1 at the cutoff of CPS <10, triple therapy with boserolimab, pembro, and chemo had acceptable safety and showed preliminary evidence of antitumor activity regardless of baseline TcellinfGEP expression or TMB status.

P1/2, N=33, Completed, Craig L Slingluff, Jr | Recruiting --> Completed

Immune cells from pmel-1 mice were isolated, activated with gp100, and cultured in vitro with 100 IU/mL IL-2 and single, dual, or triple therapy with CD27Ag, cobimetinib (MEKi) and/or αPD-L1... CD27 agonism prevents the impairment of T cell activation that was mediated by MEKi. Moreover, this CD27Ag/MEKi/PDL1i triple therapy bolstered trafficking of T cells with stem-like, effector, or resident memory properties, in turn enhancing the antitumor response. This therapy is being evaluated in metastatic CCA patients in an ongoing Phase II clinical trial.

P2, N=52, Active, not recruiting, National Cancer Institute (NCI) | N=106 --> 52 | Trial completion date: Dec 2023 --> Oct 2024 | Trial primary completion date: Dec 2023 --> May 2023

P2a, N=26, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Trial completion date: Jan 2023 --> Mar 2024

The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.

P2, N=43, Active, not recruiting, Annick Desjardins, MD | Recruiting --> Active, not recruiting | N=80 --> 43

P2, N=64, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P1, N=27, Completed, Celldex Therapeutics | Active, not recruiting --> Completed

P1, N=16, Active, not recruiting, Rutgers, The State University of New Jersey | Trial completion date: Jun 2023 --> Apr 2024

P1/2, N=30, Recruiting, Craig L Slingluff, Jr | Trial completion date: Feb 2023 --> Sep 2024 | Trial primary completion date: Feb 2023 --> Sep 2023

P1, N=14, Active, not recruiting, Nicholas Butowski | Trial completion date: Dec 2022 --> Dec 2030

Finally, we validated the superior antitumor capacity of the CEA28BB27Z CAR-T cells in xenograft models. Our findings suggest that CD27 co-stimulation signals play a key role in improving the anti-tumor efficacy of CAR-T cells.

When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination... Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.

P2, N=80, Recruiting, Annick Desjardins, MD | Suspended --> Recruiting

P2, N=106, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

P2, N=80, Suspended, Annick Desjardins, MD | Recruiting --> Suspended

P2a, N=26, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Trial completion date: Sep 2022 --> Jan 2023

Previous studies have demonstrated tumor growth inhibition with anti-CD27 agonistic monoclonal antibodies in different mice models for solid and hematological tumors...Preliminary experiments performed in human CD27 KI mice have demonstrated a long half-life of our antibody at different concentrations. Conclusions Epitope characterization, NHP pharmacokinetic analysis and additional in vivo studies of our lead anti-CD27 antibody in different tumor models use as a single agent and in combination with different check-point inhibitors are on-going.

P1, N=15, Active, not recruiting, Rutgers, The State University of New Jersey | Recruiting --> Active, not recruiting

P2, N=106, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

Varlilumab and nivolumab were well tolerated, without significant toxicity beyond that expected for each agent alone. Clinical activity was observed in patients that are typically refractory to anti-PD-1 therapy, however, overall was not greater than expected for nivolumab monotherapy. Treatment was associated with proinflammatory changes in the tumor microenvironment, particularly in ovarian cancer where the changes were associated with better clinical outcomes.

P1, N=15, Recruiting, Rutgers, The State University of New Jersey | Trial primary completion date: Dec 2021 --> Dec 2022

P1/2, N=30, Recruiting, Craig L Slingluff, Jr | Trial completion date: Mar 2022 --> Feb 2023 | Trial primary completion date: Jan 2022 --> Feb 2023

P2, N=106, Suspended, National Cancer Institute (NCI) | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022

P2, N=106, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Combined rituximab and varlilumab administration is safe in relapsed/refractory B-cell lymphomas and demonstrates efficacy in patients with T-cell activated tumours. Transcriptomic analysis of pre- and post-treatment samples confirms that varlilumab has in vivo agonistic activity. B-cell depletion by rituximab is dependent on intratumoral macrophages and varlilumab induces myeloid cell activation via a T-cell dependent, MIF signalling pathway.

P2a, N=26, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Recruiting --> Active, not recruiting | N=40 --> 26

P1, N=14, Active, not recruiting, Nicholas Butowski | Recruiting --> Active, not recruiting | N=30 --> 14

P1, N=30, Recruiting, Nicholas Butowski | Trial completion date: Jun 2021 --> Dec 2022 | Trial primary completion date: Jun 2021 --> Dec 2022

Conclusion We observed increased T cell activation and immune checkpoints immediately post-surgery with returns to baseline by week 6. These results suggest that immune checkpoint inhibitors such as anti-PD-1 may be beneficial immediately post-surgery to maintain T cell activation and prevent exhaustion of this increased population of activated T cells observed immediately post-surgery.

Conclusion We observed increased T cell activation and immune checkpoints immediately post-surgery with returns to baseline by week 6. These results suggest that immune checkpoint inhibitors such as anti-PD-1 may be beneficial immediately post-surgery to maintain T cell activation and prevent exhaustion of this increased population of activated T cells observed immediately post-surgery.

Conclusion We observed increased T cell activation and immune checkpoints immediately post-surgery with returns to baseline by week 6. These results suggest that immune checkpoint inhibitors such as anti-PD-1 may be beneficial immediately post-surgery to maintain T cell activation and prevent exhaustion of this increased population of activated T cells observed immediately post-surgery.

Conclusion We observed increased T cell activation and immune checkpoints immediately post-surgery with returns to baseline by week 6. These results suggest that immune checkpoint inhibitors such as anti-PD-1 may be beneficial immediately post-surgery to maintain T cell activation and prevent exhaustion of this increased population of activated T cells observed immediately post-surgery.