CDX-527 / Celldex - LARVOL DELTA

Therapeutic Potential of Bispecific Antibodies in Adenocarcinoma: A Targeted Literature Review (ISPOR-EU 2025) - "Molecules more frequently studied are AK104 (PD-1/CTLA-4 bispecific), zanidatamab (anti-HER2), and CDX-527 (PD-L1/CD27)...In hepatocellular carcinoma, AK104 plus lenvatinib achieved a disease control rate (DCR) of 77.8%... Our findings indicate promising efficacy of BsAbs in gastric, hepatic, and HER2-positive adenocarcinomas, with encouraging disease control and survival outcomes. While most TRAEs were manageable, frequent higher-grade events highlight the need for close monitoring. Biomarker-enriched trials may help optimize safety and patient selection."

IO biomarker • Review • Gastroesophageal Junction Adenocarcinoma • Hepatocellular Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • CD27 • CTLA4 • PD-1 • PD-L1

CDX527-01: A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=27 | Completed | Sponsor: Celldex Therapeutics | Active, not recruiting ➔ Completed

Metastases • Trial completion • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

CDX527-01: A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Celldex Therapeutics | Trial primary completion date: Jan 2023 ➔ Apr 2023

Metastases • Trial primary completion date • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

[VIRTUAL] CDX527-01, a phase 1 dose-escalation and expansion study of the PD-L1xCD27 bispecific antibody CDX-527 in patients with advanced malignancies (SITC 2020) - P1 | "Biomarker assessments will include characterizing the effects on peripheral blood immune cells and cytokines, and for the expansion cohorts, the impact of CDX-527 on the tumor microenvironment. Results N/A Conclusions N/A"

Clinical • IO Biomarker • P1 data • Oncology • Solid Tumor • CD27 • CD70

CDX527-01: A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Celldex Therapeutics | Recruiting ➔ Active, not recruiting | N=40 ➔ 27 | Trial completion date: Mar 2024 ➔ Mar 2023

Enrollment change • Enrollment closed • Trial completion date • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=96; Recruiting; Sponsor: Celldex Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Gynecologic Cancers • Head and Neck Cancer • Liver Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Thoracic Cancer • Urothelial Cancer

Bispecific Antibodies Can Drive Synergistic Immune Activation through Simultaneous Engagement of Multiple Immune Targets (PEGS 2022) - "CDX-527 is a clinical-stage bispecific antibody that is designed to simultaneously relieve PD-(L)1 suppression by inhibiting PD-L1 and stimulate CD27 to induce further T-cell activation. CDX-585 is a preclinical bispecific antibody candidate designed to inhibit myeloid suppression through ILT4/LILRB2 and overcome T cell suppression through PD-1 inhibition. Both bsAbs have demonstrated synergistic activity relative to the combination of individual parental mAbs in cultured immune assays and exhibited anti-tumor activity in animal models. The design, development and preclinical characterization of these bispecifics will be presented."

Oncology • CD27

CDX527-01: A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Celldex Therapeutics | Trial completion date: Jan 2023 ➔ Mar 2024 | Trial primary completion date: Mar 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

Celldex Reports Third Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "In the Phase 1 study of CDX-1140 in up to ~260 patients with recurrent, locally advanced or metastatic solid tumors and B cell lymphomas, the monotherapy cohort, the combination cohort with CDX-301 and the safety run-in combination cohort with gemcitabine/nab-paclitaxel have been completed....The combination of CDX-1140 with pembrolizumab has completed the safety run-in phase. Expansion cohorts in patients with checkpoint-refractory/resistant squamous cell head and neck cancer and non-small cell lung cancer are enrolling patients....The expansion is designed to further evaluate the tolerability, and biologic and anti-tumor effects of selected dose level of CDX-527 in specific tumor types. Enrollment to the dose escalation portion of the study has been completed and an expansion cohort in ovarian cancer is currently enrolling patients."

Enrollment status • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] CDX527-01, a phase 1 dose-escalation and expansion study of the PD-L1xCD27 bispecific antibody CDX-527 in patients with advanced malignancies (SITC 2020) - P1 | "Biomarker assessments will include characterizing the effects on peripheral blood immune cells and cytokines, and for the expansion cohorts, the impact of CDX-527 on the tumor microenvironment. Results N/A Conclusions N/A"

Clinical • IO Biomarker • P1 data • Oncology • Solid Tumor • CD27 • CD70

[VIRTUAL] A phase 1 dose-escalation study of a PD-L1xCD27 bispecific antibody CDX-527 in patients with advanced malignancies. (ASCO 2021) - P1 | "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 • IO biomarker • P1 data • Fatigue • Immune Modulation • Infectious Disease • Inflammation • Musculoskeletal Pain • Oncology • Respiratory Diseases • Solid Tumor • CD27

Celldex Reports Second Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - “CDX-1140 - CD40 Agonist Program:An update from this program is expected by end of 2021; CDX-527 - Bispecific Antibody Program: In June, Celldex reported initial data from the Phase 1 dose-escalation study in up to ~40 patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy to be followed by tumor-specific expansion cohorts, which were presented at the 2021 ASCO Annual Meeting…additional data is expected in 2022.”

Clinical • P1 data • Oncology • Solid Tumor

Celldex Presents Preliminary Data from Ongoing CDX-527 Phase 1 Dose Escalation Trial at the 2021 ASCO Annual Meeting (GlobeNewswire) - P1, N=40; NCT04440943; Sponsor: Celldex Therapeutics; "Celldex Therapeutics, Inc...announced preliminary data from the Company’s Phase 1 dose escalation study of PD-L1xCD27 bispecific antibody CDX-527 in patients with advanced malignancies. These data were presented in a poster session as part of the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting taking place June 4-8, 2021...CDX-527 was well tolerated, with no dose-limiting toxicities or treatment related serious adverse events observed...Celldex expects to report additional safety, PK, PD and clinical activity data from this study during 2022."

P1 data • Oncology • Solid Tumor

Celldex Provides Corporate Update and Reports Fourth Quarter and Year End 2020 Results (GlobeNewswire) - “CDX-1140 with KEYTRUDA® (pembrolizumab) in patients who have progressed on checkpoint therapy; and A combination of CDX-1140 with standard of care chemotherapy in first line metastatic pancreatic cancer. Updated data from this program are expected to be presented later this year; CDX-527…In August 2020, Celldex initiated a Phase 1 dose-escalation study in up to ~90 patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy to be followed by tumor-specific expansion cohorts…Initial data from the Phase 1 study are expected to be presented later this year.”

P1 data • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

CDX527-01: A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Celldex Therapeutics; N=96 ➔ 40; Trial completion date: Apr 2022 ➔ Jan 2023

Clinical • Enrollment change • Trial completion date • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

Celldex Provides Corporate Update and Reports Third Quarter 2020 Results (Celldex Press Release) - "Updated interim data from the ongoing Phase 1 study has been accepted for poster presentation at the Society for Immunotherapy of Cancer’s (SITC) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) and will include updated data from the monotherapy and CDX-301 combination cohorts focusing on the MTD level (1.5 mg/kg), as well as preliminary safety data from the combination cohort with pembrolizumab....The CDX-527 Phase 1 study design will be presented as a clinical trial in progress poster at SITC 2020."

Clinical protocol • P1 data • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Celldex Presents Data from Oncology Portfolio at SITC 2020 (GlobeNewswire) - "CDX-527 Presentation Highlights (Poster #406):...In August 2020, Celldex initiated a multi-center Phase 1 dose-escalation study in up to ~90 patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy to be followed by tumor-specific expansion cohorts. The study is designed to determine the MTD during a dose-escalation phase and to recommend a dose level for further study in the subsequent expansion phase. The expansion is designed to further evaluate the tolerability, and biologic and anti-tumor effects of selected dose level(s) of CDX-527 in specific tumor types. Enrollment is ongoing and initial data from the Phase 1 study are anticipated in the first half of 2021."

Clinical protocol • Enrollment open • P1 data • Oncology • Solid Tumor

Development of CDX-527: a bispecific antibody combining PD-1 blockade and CD27 costimulation for cancer immunotherapy. (PubMed, Cancer Immunol Immunother) - "A pilot study of CDX-527 in cynomolgus macaques confirmed a mAb-like pharmacokinetic profile without noted toxicities. These studies demonstrate that CDX-527 effectively combines PD-1 blockade and CD27 costimulation into one molecule that is more potent than combination of the parental antibodies providing the rationale to advance this BsAb toward clinical studies in cancer patients."

Journal • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Oncology

Celldex Therapeutics Initiates Phase 1 Study of New Bispecific Product Candidate CDX-527 in Solid Tumors (GlobeNewswire) - "Celldex Therapeutics, Inc…announced today that enrollment has opened in its open-label, Phase 1 study of CDX-527 in patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy….This study, which is expected to enroll up to approximately 90 patients with solid tumors, is designed to determine the maximum tolerated dose, or MTD, during a dose-escalation phase and to recommend a dose level for further study in a subsequent expansion phase."

Enrollment open • Oncology • Solid Tumor

"#CelldexTherapeutics Initiates Phase 1 Study of New Bispecific Product Candidate #CDX527 in #SolidTumors $CLDX https://t.co/74Gfy7GavZ" (@1stOncology)

Oncology • Solid Tumor

[VIRTUAL] Development of CDX-527, a Novel Bispecific-Immune Modulating Antibody Targeting PD-L1 and CD27 (PEGS 2020) - "CD27 is a costimulatory molecule providing a complementary target to the PD-1/PD-L1 axis on T cells. A tetravalent format was selected for CDX-527, that along with potent PD-1 blockade, provides efficient cross-linking, which is important for CD27 agonistic activity by allowing interaction with both Fc-receptor and PD-L1-bearing cells."

Immune Modulation • Inflammation • Oncology • CD27

Celldex Provides Corporate Update and Reports Second Quarter 2020 Results (Celldex Press Release) - "A combination of CDX-1140 with standard of care chemotherapy in first line metastatic pancreatic cancer is expected to initiate later this year. A data update from the ongoing Phase 1 study is planned for presentation in the fall of 2020. CDX-527…Celldex anticipates initiating a Phase 1 dose-escalation study in up to ~90 patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy later this year to be followed by tumor-specific expansion cohorts."

New P1 trial • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=96; Not yet recruiting; Sponsor: Celldex Therapeutics

Clinical • New P1 trial • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Thoracic Cancer • Urothelial Cancer