CDX-1140 / Celldex - LARVOL DELTA

Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2025 ➔ Aug 2026

Enrollment open • IO biomarker • Trial initiation date • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Nasopharyngeal Carcinoma • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Phase I pilot of pegylated liposomal doxorubicin, CD40 agonist antibody CDX-1140, and Flt3 ligand CDX-301 in advanced HER2-negative breast cancer (SABCS 2025) - P1 | "As of June 24th, 2025 this trial is in dose expansion and has enrolled 23 of 30 evaluable patients (NCT05029999). The trial is currently open at University of Texas Southwestern Simmons Comprehensive Cancer Center, University of Chicago, University of Texas San Antonio Health Science Center, Johns Hopkins, and University of North Carolina."

Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD40 • CD8 • HER-2

Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer (clinicaltrials.gov) - P2 | N=44 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2027 ➔ Nov 2027 | Trial primary completion date: May 2027 ➔ Nov 2027

IO biomarker • Trial completion date • Trial primary completion date • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Nasopharyngeal Carcinoma • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Hotspot TCR-T: A Phase I/Ib Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T) (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Providence Health & Services | Trial primary completion date: Aug 2025 ➔ Dec 2025

Trial primary completion date • Oncology • CD4

Hotspot TCR-T: A Phase I/Ib Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T) (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Providence Health & Services | Trial primary completion date: Feb 2025 ➔ Aug 2025

Trial primary completion date • Oncology • CD4

Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer (clinicaltrials.gov) - P2 | N=44 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

IO biomarker • New P2 trial • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Nasopharyngeal Carcinoma • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

STU-2021-0657: CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC) (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Hepatology • Oncology • Solid Tumor

A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC) (clinicaltrials.gov) - P1/2 | N=60 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Hepatology • Oncology • Solid Tumor

1B-22-2: In Situ Immunomodulation with CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients W/ Unresectable and Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: University of Southern California | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Immunomodulating • Metastases • Trial completion date • Trial primary completion date • Basal Cell Carcinoma • Breast Cancer • HER2 Breast Cancer • Immunology • Melanoma • Merkel Cell Carcinoma • Oncology • Osteosarcoma • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • HER-2

Phase I trial of pegylated liposomal doxorubicin chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic HER2 negative breast cancer (SABCS 2024) - P1 | " This is a single arm phase I pilot study of the combination of liposomal doxorubicin, CDX-1140 (CD40 agonist monoclonal antibody), and CDX-301 (recombinant Flt3 ligand) in patients with metastatic or unresectable locally advanced HER2 negative breast cancer. Key eligibility criteria are unresectable stage III or stage IV HER2 negative breast cancer, for TNBC up to 3 prior therapies for metastatic disease allowed, for HR+ disease prior cyclin dependent kinase 4/6 inhibitors required and up to 3 prior lines of chemotherapy and/or antibody drug conjugates for metastatic disease allowed, measurable disease by RECIST 1.1 criteria, consent for pre- and on-treatment biopsies of tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing (neo)adjuvant anthracycline-based therapy, and no history of non-infectious..."

Combination therapy • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD40 • HER-2

Personalized TCR-T: Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T) (clinicaltrials.gov) - P1 | N=1 | Active, not recruiting | Sponsor: Providence Health & Services | Enrolling by invitation ➔ Active, not recruiting | N=24 ➔ 1

Enrollment change • Enrollment closed • Tumor-specific neoantigens • Oncology • CD4

Phase I/II clinical trial of a melanoma vaccine targeting shared nonmutated antigens and a shared mutated neoantigen with an agonistic CD40 antibody (CDX-1140) plus TLR agonist (polyICLC) (SITC 2024) - P1/2 | "Strong responses to the mNeoAg BRAF peptide were evident at weeks 6 and 9. Error bars = SD"

Clinical • IO biomarker • Late-breaking abstract • P1/2 data • Tumor-specific neoantigens • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • CD40 • IFNG

Engineering T cells with CD40-based chimeric receptors to enhance adoptive T cell therapy (SITC 2024) - "Thus, we hypothesize that overexpression of CD40 or CD40 chimeric receptors can increase antitumor T-cell function when CD40 is engaged by an agonistic anti-CD40 antibody (CDX-1140, Celldex Therapeutics)...Overall, our study highlights the potential of CD40 gene engineering to enhance adoptive cell therapy. Additional characterization of our lead CD40-based receptors is ongoing."

IO biomarker • Colorectal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD40 • CD40LG • HLA-C • IFNG • IL2RA • KRAS • STAT5

Phase 1b study of maintenance soluble beta-glucan (Odetiglucan) in combination with a CD40 agonistic monoclonal antibody (CDX-1140) in patients with metastatic pancreatic adenocarcinoma that had not progressed on first-line chemotherapy (AACRPanCa 2024) - "The combination of odetiglucan and CDX-1140 was feasible and safe when administered as maintenance therapy in patients with mPDAC whose disease had not progressed on 1L chemotherapy. Treatment produced encouraging activity with changes in immunological correlates associated with disease control. These early results support further investigation combining odetiglucan with a CD40 agonist in mPDAC."

Clinical • Combination therapy • Metastases • P1 data • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Leukopenia • Musculoskeletal Pain • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40 • CD8 • CLEC7A • ITGAM

Phase 1b study of maintenance soluble beta-glucan (Odetiglucan) in combination with a CD40 agonistic monoclonal antibody (CDX-1140) in patients with metastatic pancreatic adenocarcinoma that had not progressed on first-line chemotherapy* (AACRPanCa 2024) - "The combination of odetiglucan and CDX-1140 was feasible and safe when administered as maintenance therapy in patients with mPDAC whose disease had not progressed on 1L chemotherapy. Treatment produced encouraging activity with changes in immunological correlates associated with disease control. These early results support further investigation combining odetiglucan with a CD40 agonist in mPDAC."

Clinical • Combination therapy • Metastases • P1 data • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Leukopenia • Musculoskeletal Pain • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40 • CD8 • CLEC7A • ITGAM

Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma) (clinicaltrials.gov) - P1/2 | N=22 | Completed | Sponsor: Craig L Slingluff, Jr | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Mar 2024 | Trial primary completion date: Sep 2024 ➔ Mar 2024

Trial completion • Trial completion date • Trial primary completion date • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • CD4

CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | N=45 ➔ 30

Combination therapy • Enrollment change • Metastases • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A phase 1 trial in progress for in situ immunomodulation with CDX-301, radiation therapy, poly-ICLC, and CDX-1140 in patients with unresectable and metastatic solid tumors. (ASCO 2024) - P1 | "4. Scientific Reports 2022."

Clinical • Immunomodulating • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Melanoma • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CD40 • FLT3 • HER-2 • TLR3

A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC) (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

A Maintenance Therapy Study of Odetiglucan With CDX-1140 in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: HiberCell, Inc. | N=45 ➔ 5 | Trial completion date: Apr 2027 ➔ Mar 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Mar 2024; sponsor decision

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: Washington University School of Medicine | N=24 ➔ 16 | Trial completion date: Mar 2024 ➔ Nov 2023 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2024 ➔ Nov 2023; Celldex decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 for the Treatment of Patients With Recurrent Ovarian Cancer (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Roswell Park Cancer Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

Harnessing the potential of CD40 agonism in cancer therapy. (PubMed, Cytokine Growth Factor Rev) - "In this review, we present the current understanding of the mechanism of action for CD40, along with results from the clinical development of agonistic human CD40 antibodies in cancer treatment (selicrelumab, CDX-1140, APX005M, mitazalimab, 2141-V11, SEA-CD40, LVGN7409, and bispecific antibodies). This review also examines the safety profile of CD40 agonists in both preclinical and clinical settings, highlighting optimized dosage levels, potential adverse effects, and strategies to mitigate them."

IO biomarker • Journal • Review • Oncology • CD40 • CD40LG • CD8 • TNFA

Phase I trial of pegylated liposomal doxorubicin chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer (SABCS 2023) - P1 | " This is a single arm phase I pilot study of liposomal doxorubicin, CDX-1140 (CD40 agonist monoclonal antibody), and CDX-301 (recombinant Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic TNBC. Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line treatment for metastatic disease (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites..."

Combination therapy • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD40 • HER-2 • PD-L1