Mobista (CDX-301) / Celldex - LARVOL DELTA

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in Melanoma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Jan 2027 ➔ Sep 2030 | Trial primary completion date: Jan 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer. (PubMed, Clin Cancer Res) - P1 | "Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity. Pre-existing rather than treatment-induced immune activation was associated with clinical benefit across cohorts, highlighting the importance of baseline immune fitness."

Journal • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TNFA

Revitalizing systemic immune responses in advanced NSCLC using FLT3L and SBRT. (PubMed, medRxiv) - "Here, we report the results of a Phase II clinical trial where twenty-nine patients with advanced, previously treated NSCLC were treated with stereotactic body radiotherapy (SBRT) targeting a single site of disease along with CDX-301, a recombinant human Fms-like tyrosine kinase 3 ligand (FLT3L)...These coordinated immune responses were sustained for over 4 weeks in responders, highlighting a potential therapeutic axis engaged in a systemic immune response against multiple lesions in NSCLC. Overall, these findings underscore the potential of combining in situ vaccination, using SBRT, with strategies to enhance the activation of innate immune cells, such as DCs through FLT3L, to potentiate robust anti-tumor T cell responses."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • FLT3 • IL12A

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer (Clin Cancer Res) - P1 | N=43 | PORTER (NCT03835533) | "43 patients enrolled (N = 14, 15, 14 in Cohorts A, B, C). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 10 (71%), 2 (13%), and 2 (14%) patients, respectively, with one Grade 5 TRAE in Cohort A. Composite response rates were 7% (1/14), 33% (5/15), and 7% (1/14). Across cohorts, 6-month disease control was associated with pre-existing memory/regulatory T cells, TNFα, and other inflammatory pathways....Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity."

P1 data • Castration-Resistant Prostate Cancer

FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=33 | Completed | Sponsor: Albert Einstein College of Medicine | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • 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

PGV-Prostate: The Safety and Tolerability of PGV001-based Personalized Multi-peptide Vaccines in the Adjuvant Setting. (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Ashutosh Kumar Tewari | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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

FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Albert Einstein College of Medicine | Completed ➔ Active, not recruiting | Trial completion date: Oct 2022 ➔ Oct 2024

Enrollment closed • Metastases • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Minimal PBPK/PD Model with Expansion-Enhanced Target-Mediated Drug Disposition to Support a First-in-Human Clinical Study Design for a FLT3L-Fc Molecule. (PubMed, Pharmaceutics) - "In addition to the preclinical PK data of FLT3L-Fc in cynomolgus monkeys, clinical PK and PD data from other FLT3-agonist molecules (GS-3583 and CDX-301) were used to inform the model and project the expansion profiles of conventional DC1s (cDC1s) and total DCs in peripheral blood. This work constitutes an essential part of our model-informed drug development (MIDD) strategy for clinical development of FLT3L-Fc by projecting PK/PD in healthy volunteers, determining the first-in-human (FIH) dose, and informing the efficacious dose in clinical settings. Model-generated results were incorporated in regulatory filings to support the rationale for the FIH dose selection."

Journal • P1 data • FLT3

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in Melanoma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Dana-Farber Cancer Institute | N=20 ➔ 30

Combination therapy • Enrollment change • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

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

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

Revitalizing systemic immune responses in progressive NSCLC using FLT3L and SBRT (SITC 2023) - "Subcutaneous CDX-301 (75 µg/kg) was administered daily for five days with concomitant treatment of SBRT (figure 1)...Patients with abscopal responses exhibit distinct cellular responses to FLT3L and SBRT that align with the emerging significance of DC1 and CD4 T cells. This sustained Type 1 response over 4 weeks in abscopal responders independent of high grade adverse events, indicating a unique therapeutic axis to harness systemic immunity against metastatic lesions in NSCLC."

Late-breaking abstract • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • FLT3 • IL21

Antigen-loaded Monocyte Administration and Flt3 Ligand Augment the Antitumor Efficacy of Immune Checkpoint Blockade in a Murine Melanoma Model. (PubMed, J Immunother) - "In this study, we investigated whether monocyte vaccination in combination with CDX-301, a DC-expanding cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), could improve the antitumor efficacy of anti-programmed cell death (anti-PD-1) immune checkpoint blockade...To our knowledge, this is the first demonstration that a cancer vaccine strategy and Flt3L can improve the antitumor efficacy of anti-PD-1. The findings presented here warrant further study of how monocyte vaccines can improve Flt3L and immune checkpoint blockade as they enter clinical trials."

Checkpoint block • Checkpoint inhibition • Journal • Preclinical • Melanoma • Oncology • Solid Tumor • FLT3

FLT3 Ligand, CD40 Agonist Antibody, and Stereotactic Radiotherapy (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Albert Einstein College of Medicine | N=46 ➔ 5 | Trial completion date: Aug 2024 ➔ Aug 2022 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Aug 2022; Low accrual

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Apr 2026 ➔ Apr 2025

Combination therapy • Metastases • Trial completion date • Breast Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Phase 1 pilot study with dose expansion of chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer. (ASCO 2022) - P1 | " This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic triple-negative breast cancer. Key eligibility criteria are unresectable stage III or stage IV triple-negative breast cancer (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (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."

Clinical • Combination therapy • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Immune Modulation • Inflammation • Oncology • Pneumonia • Solid Tumor • Triple Negative Breast Cancer • CD40 • HER-2 • PD-L1

Converting HR+ Breast Cancer Into an Individualized Vaccine (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Weill Medical College of Cornell University | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

[VIRTUAL] CDX1140-01, a Phase 1 dose-escalation/expansion study of CDX-1140 alone (Part 1) and in combination with CDX-301 (Part 2) or pembrolizumab (Part 3) (SITC 2020) - P1 | "Transaminitis and CRS have generally been low grade and infrequent. A cohort combining CDX-1140 with chemotherapy will be initiated in patients with previously untreated metastatic pancreatic adenocarcinoma."

Combination therapy • IO biomarker • P1 data • Follicular Lymphoma • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Lymphoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Phase 1 trial of anthracycline chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer (SABCS 2022) - P1 | "CDX-301 will be discontinued after 2 cycles; liposomal-doxorubicin and CDX-1140 will be continued until disease progression or clinically limiting toxicities. Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (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 (NCT05029999)."

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

NeoVax + CDX-301 and Nivolumab in Melanoma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Jan 2023 ➔ Jan 2025

Trial primary completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Vaccination With Flt3L, Radiation, and Poly-ICLC (clinicaltrials.gov) - P1/2 | N=56 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Trial completion date: Mar 2026 ➔ Mar 2025 | Trial primary completion date: Mar 2026 ➔ Mar 2025

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Head and Neck Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck