varlilumab (CDX 1127)

P1/2, N=26, Completed, University Hospital Southampton NHS Foundation Trust | Active, not recruiting --> Completed | Phase classification: P2a --> P1/2 | Trial completion date: Mar 2024 --> Aug 2024

P2, N=54, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

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=33, Completed, Craig L Slingluff, Jr | Recruiting --> Completed

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=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

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

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

Clinical studies demonstrated the safety and biological activity of combining varlilumab, an agonist anti-CD27 mAb, with nivolumab or atezolizumab, along with modest clinical activity of the combinations . Preliminary results indicate that the novel anti-PD-L1xCD27 bispecific antibody CDX-527 up to and including the 1 mg/kg dose level has been well tolerated . Additional data will be presented, including the safety profile at higher dose levels along with clinical activity, as well as PK and PD data.

P1/2, N=30, Recruiting, Craig L Slingluff, Jr | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Jan 2021 --> Jan 2022

P2, N=106, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021

P2a, N=40, Recruiting, University Hospital Southampton NHS Foundation Trust | Trial completion date: Oct 2020 --> Sep 2022 | Trial primary completion date: Dec 2019 --> Mar 2021

These data support further investigation of varlilumab for hematologic malignancies, particularly in combination approaches targeting nonredundant immune regulating pathways. This trial was registered at www.clinicaltrials.gov as #NCT01460134.

P2, N=106, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Dec 2019 --> Dec 2020