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DRUG:

varlilumab (CDX 1127)

i
Other names: CDX 1127, CDX-1127, CD27 mAb, CDX1127
Company:
Celldex
Drug class:
T-cell stimulant, CD27 agonist
3ms
A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic NSCLC. (PubMed, JTO Clin Res Rep)
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 data • Journal • Combination therapy • Metastases
|
CD27 (CD27 Molecule)
|
Tecentriq (atezolizumab) • varlilumab (CDX 1127)
5ms
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov)
P1, N=14, Terminated, Nicholas Butowski | Active, not recruiting --> Terminated; Industry sponsor decision
Trial termination
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC) • IMA950
9ms
Trial completion
|
CD4 (CD4 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC)
1year
DIAL: Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas (clinicaltrials.gov)
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
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
BCL6 rearrangement • BCL2 rearrangement
|
Opdivo (nivolumab) • varlilumab (CDX 1127) • ABP 206 (nivolumab biosimilar)
1year
RiVa: A Combination of Rituximab and Varlilumab Immunotherapy in Patients With B-cell Lymphoma (clinicaltrials.gov)
P2a, N=26, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Trial completion date: Jan 2023 --> Mar 2024
Trial completion date
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 expression
|
Rituxan (rituximab) • varlilumab (CDX 1127)
1year
A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas. (PubMed, Neuro Oncol)
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.
Journal
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CD27 (CD27 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC) • IMA950
over1year
DERIVe: DC Migration Study to Evaluate TReg Depletion In GBM Patients With and Without Varlilumab (clinicaltrials.gov)
P2, N=43, Active, not recruiting, Annick Desjardins, MD | Recruiting --> Active, not recruiting | N=80 --> 43
Enrollment closed • Enrollment change
|
MGMT (6-O-methylguanine-DNA methyltransferase) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3) • CCL3 (C-C Motif Chemokine Ligand 3) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
|
temozolomide • varlilumab (CDX 1127)
over1year
Enrollment closed • Metastases
|
Tecentriq (atezolizumab) • Cotellic (cobimetinib) • varlilumab (CDX 1127)
over1year
Atezolizumab and Varlilumab in Combination With Radiation Therapy for NSCLC (clinicaltrials.gov)
P1, N=16, Active, not recruiting, Rutgers, The State University of New Jersey | Trial completion date: Jun 2023 --> Apr 2024
Trial completion date • Combination therapy • Metastases
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • LAG3 (Lymphocyte Activating 3) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD27 (CD27 Molecule)
|
BRAF V600E • EGFR mutation • BRAF V600 • EGFR T790M • ALK rearrangement • ROS1 rearrangement
|
Tecentriq (atezolizumab) • varlilumab (CDX 1127)
over1year
Mel-65: Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma (clinicaltrials.gov)
P1/2, N=30, Recruiting, Craig L Slingluff, Jr | Trial completion date: Feb 2023 --> Sep 2024 | Trial primary completion date: Feb 2023 --> Sep 2023
Trial completion date • Trial primary completion date
|
CD4 (CD4 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC)
over1year
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov)
P1, N=14, Active, not recruiting, Nicholas Butowski | Trial completion date: Dec 2022 --> Dec 2030
Trial completion date
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
HLA-A2 positive
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC) • IMA950
over1year
Sensitizing breast cancers to immune checkpoint inhibitors through CD27 agonism and vaccination against tumor-associated antigen (AACR 2023)
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.
Checkpoint inhibition
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HER-2 (Human epidermal growth factor receptor 2) • CD27 (CD27 Molecule)
|
CD27 expression
|
varlilumab (CDX 1127)
over1year
Enrollment open
|
MGMT (6-O-methylguanine-DNA methyltransferase) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3) • CCL3 (C-C Motif Chemokine Ligand 3) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
|
temozolomide • varlilumab (CDX 1127)
almost2years
DIAL: Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
BCL6 rearrangement • BCL2 rearrangement
|
Opdivo (nivolumab) • varlilumab (CDX 1127)
almost2years
Trial suspension
|
MGMT (6-O-methylguanine-DNA methyltransferase) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
|
temozolomide • varlilumab (CDX 1127)
2years
RiVa: A Combination of Rituximab and Varlilumab Immunotherapy in Patients With B-cell Lymphoma (clinicaltrials.gov)
P2a, N=26, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Trial completion date: Sep 2022 --> Jan 2023
Trial completion date
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 expression
|
Rituxan (rituximab) • varlilumab (CDX 1127)
2years
Atezolizumab and Varlilumab in Combination With Radiation Therapy for NSCLC (clinicaltrials.gov)
P1, N=15, Active, not recruiting, Rutgers, The State University of New Jersey | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • LAG3 (Lymphocyte Activating 3) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD27 (CD27 Molecule)
|
BRAF V600E • EGFR mutation • BRAF V600 • EGFR T790M • ALK rearrangement • ROS1 rearrangement
|
Tecentriq (atezolizumab) • varlilumab (CDX 1127)
2years
DIAL: Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas (clinicaltrials.gov)
P2, N=106, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
Enrollment closed • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
BCL6 rearrangement • BCL2 rearrangement
|
Opdivo (nivolumab) • varlilumab (CDX 1127)
2years
Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors. (PubMed, J Immunother Cancer)
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.
Journal • Combination therapy
|
PD-L1 (Programmed death ligand 1) • CD27 (CD27 Molecule)
|
Opdivo (nivolumab) • varlilumab (CDX 1127)
over2years
Atezolizumab and Varlilumab in Combination With Radiation Therapy for NSCLC (clinicaltrials.gov)
P1, N=15, Recruiting, Rutgers, The State University of New Jersey | Trial primary completion date: Dec 2021 --> Dec 2022
Trial primary completion date • Combination therapy
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • LAG3 (Lymphocyte Activating 3) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD27 (CD27 Molecule)
|
BRAF V600E • EGFR mutation • BRAF V600 • EGFR T790M • ALK rearrangement • ROS1 rearrangement
|
Tecentriq (atezolizumab) • varlilumab (CDX 1127)
over2years
Mel-65: Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma (clinicaltrials.gov)
P1/2, N=30, Recruiting, Craig L Slingluff, Jr | Trial completion date: Mar 2022 --> Feb 2023 | Trial primary completion date: Jan 2022 --> Feb 2023
Trial completion date • Trial primary completion date
|
CD4 (CD4 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC)
almost3years
Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas (clinicaltrials.gov)
P2, N=106, Suspended, National Cancer Institute (NCI) | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
Trial completion date • Trial primary completion date • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
BCL6 rearrangement • BCL2 rearrangement
|
Opdivo (nivolumab) • varlilumab (CDX 1127)
3years
Trial suspension • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
BCL6 rearrangement • BCL2 rearrangement
|
Opdivo (nivolumab) • varlilumab (CDX 1127)
3years
Clinical and Biological Effects of Combined CD27 and CD20 Antibody Therapy in Relapsed/Refractory B-Cell Lymphoma: The Riva Trial (ASH 2021)
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.
Clinical
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CD8 (cluster of differentiation 8) • CD74 (CD74 Molecule) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD44 (CD44 Molecule) • CD14 (CD14 Molecule) • CD27 (CD27 Molecule) • CD86 (CD86 Molecule)
|
Rituxan (rituximab) • varlilumab (CDX 1127)
over3years
RiVa: A Combination of Rituximab and Varlilumab Immunotherapy in Patients With B-cell Lymphoma (clinicaltrials.gov)
P2a, N=26, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Recruiting --> Active, not recruiting | N=40 --> 26
Clinical • Enrollment closed • Enrollment change
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 expression
|
Rituxan (rituximab) • varlilumab (CDX 1127)
over3years
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov)
P1, N=14, Active, not recruiting, Nicholas Butowski | Recruiting --> Active, not recruiting | N=30 --> 14
Clinical • Enrollment closed • Enrollment change
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
HLA-A2 positive • HLA-A*02 positive
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC) • IMA950
over3years
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov)
P1, N=30, Recruiting, Nicholas Butowski | Trial completion date: Jun 2021 --> Dec 2022 | Trial primary completion date: Jun 2021 --> Dec 2022
Clinical • Trial completion date • Trial primary completion date
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC) • IMA950
over3years
[VIRTUAL] A phase 1 dose-escalation study of a PD-L1xCD27 bispecific antibody CDX-527 in patients with advanced malignancies. (ASCO 2021)
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.
Clinical • P1 data • PD(L)-1 Biomarker • IO biomarker
|
CD27 (CD27 Molecule)
|
Opdivo (nivolumab) • Tecentriq (atezolizumab) • varlilumab (CDX 1127) • CDX-527
almost4years
Mel-65: Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma (clinicaltrials.gov)
P1/2, N=30, Recruiting, Craig L Slingluff, Jr | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Jan 2021 --> Jan 2022
Clinical • Trial completion date • Trial primary completion date
|
CD4 (CD4 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC)
almost4years
Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas (clinicaltrials.gov)
P2, N=106, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 rearrangement • BCL2 rearrangement
|
Opdivo (nivolumab) • varlilumab (CDX 1127)
4years
RiVa: A Combination of Rituximab and Varlilumab Immunotherapy in Patients With B-cell Lymphoma (clinicaltrials.gov)
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
Clinical • Trial completion date • Trial primary completion date
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 expression
|
Rituxan (rituximab) • varlilumab (CDX 1127)
over4years
Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, for hematologic malignancies. (PubMed, Blood Adv)
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.
Clinical • Journal
|
CD70 (CD70 Molecule) • CD27 (CD27 Molecule)
|
varlilumab (CDX 1127)
almost5years
Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas (clinicaltrials.gov)
P2, N=106, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Dec 2019 --> Dec 2020
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 rearrangement • BCL2 rearrangement
|
Opdivo (nivolumab) • varlilumab (CDX 1127)