PDS0301 / EMD Serono, PDS Biotechnology - LARVOL DELTA

Phase I/II Evaluation of the Combination of Entinostat, M9241 and Bintrafusp Alfa in Patients with Advanced HPV Related Malignancies (SITC 2022) - P1/2 | "Background More than 630,000 cases of HPV related cancer (e.g. cervical, oropharyngeal, anal) occur worldwide annually. To date the triple combination appears to have a manageable safety profile along with encouraging clinical activity in patients with advanced checkpoint refractory HPV related cancers including in pts who have previously progressed on PD(L)1 inhibitor then on PDS0101, M9241 and bintrafusp alfa. Trial Registration NCT04708470"

Clinical • P1/2 data • Cervical Cancer • Oncology • Oropharyngeal Cancer • IL12A • STAT3 • TGFB1

Enzalutamide and M9241 in PET Positive Recurrent Prostate Cancer (pprPC) Without Testosterone Lowering Therapy (clinicaltrials.gov) - P2 | N=55 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4

Novel Combination Immunotherapy and Clinical Activity in Patients With HPV-Associated Cancers: A Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P1/2 | "In this trial, the combination of PDS0101, PDS01ADC, and bintrafusp alfa showed an acceptable safety profile and promising antitumor activity and improved OS in patients with HPV-16-positive cancers, in both ICB-naive and ICB-resistant patients, warranting further evaluation of the combination of PDS0101 and PDS01ADC with simultaneous PD-L1/TGF-β inhibition in these populations."

Clinical • Journal • Oncology • Solid Tumor • IL12A • TGFB1

Phase II evaluation of combination immunotherapy with CV301, N-803, bintrafusp alfa, and M9241 in patients with advanced small bowel and colorectal cancers. (ASCO-GI 2023) - P2 | "All patients had received prior 5-fluorouracil-based treatment, with 29/30 (96.7%) having received ≥ 2 lines of systemic therapy. Combination therapies with CV301, N-803, bintrafusp alfa, and M9241 had manageable safety profiles. Preliminary clinical activity was observed in patients with advanced MSS/pMMR small bowel or CRC. Median OS was promising as compared to historical median survivals of 6-7 months following receipt of multiple lines of therapy."

Clinical • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IL12A • MUC1 • TGFB1

A Phase I Single-Arm Study of Biweekly NHS-IL12 in Patients With Metastatic Solid Tumors. (PubMed, Oncologist) - P1 | "Biweekly NHS-IL12 was well tolerated in this small phase I study. Additional studies incorporating NHS-IL12 with other immunomodulating agents are underway. (ClinicalTrials.gov Identifier: NCT01417546)."

Journal • Metastases • P1 data • Immune Modulation • Inflammation • Oncology • Solid Tumor • IL12A

Short-course (3-month) enzalutamide monotherapy in biochemically recurrent prostate cancer (BCR): Preliminary prostate specific membrane antigen tumor volume (PSMA-TV) data. (ASCO-GU 2026) - P2 | " NCT06096870 is a clinical trial (n=50) at the NCI randomizing BCR pts to either enza monotherapy or enza + PDS01ADC (IL-12 immunocytokine). This is the first data presented evaluating PSMA-TV changes after enza in BCR without ADT. Despite this small data set, lack of concordance of PSA and PSMA responses should highlight a need to collect more data to better understand the clinical utility of PSMA scans in defining therapeutic response in BCR. It further indicates the need for caution in the use of PSMA imaging presumptively to define therapeutic benefit or lack thereof in clinical practice."

Monotherapy • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IL12A

WITHDRAWN: Evaluating PSA and PSMA responses of enzalutamide with or without a tumor targeting immunocytokine (PDS01ADC) in patients with PSMA-positive recurrent prostate cancer without testosterone-lowering therapy. (ASCO-GU 2025) - P2 | "Funded by Enzalutamide Drug support for the study is being provided by Astellas Pharma Global Development, Inc/Pfizer Inc and PDS01ADC is provided as part of a Collaborative Research and Development Agreement with PDS Biotechnology Corporation Clinical Trial Registration Number: NCT06096870"

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

20-C-0012: Bintrafusp Alfa (M7824) and PDS01ADC Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=100 ➔ 22 | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2027 ➔ Aug 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urology • Urothelial Cancer • CD4

A Phase II Study Evaluating T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine PDS01ADC in Localized High and Intermediate Risk Prostate Cancer Treated With Androgen Deprivation Therapy (clinicaltrials.gov) - P2 | N=65 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PD-L1

PDS Biotech Announces Strategic Refocus Prioritizing PDS0301 in Metastatic Colorectal Cancer (mCRC) and Partnership Strategy for PDS0101 (GlobeNewswire) - "We have decided that we will cease further internal investment in the PDS0101 Phase 3 VERSATILE-003 trial, including the discontinuation of the VERSATILE-003 Phase 3 trial, and intend to pursue strategic partnerships or other externally funded opportunities for the continued development of PDS0101. This decision follows a comprehensive assessment of the capital, time and resources required to complete the Phase 3 trial and support commercialization of PDS0101....A randomized Phase 2b trial with PDS0301 has been designed taking into account feedback received from the FDA and is intended to generate meaningful clinical data with disciplined capital investment."

Pipeline update • Trial termination • Squamous Cell Carcinoma of Head and Neck

Cytokine delivery and targeting strategies in pet dogs with cancer: a comparative immuno-oncology approach. (PubMed, Front Immunol) - "This mini review examines targeted cytokine delivery platforms evaluated in pet dogs with naturally occurring malignancies, including aluminum hydroxide-anchored IL-12, collagen-binding IL-2/IL-12 fusion proteins, antibody-cytokine immunocytokines (NHS-IL12 and hu14.18-IL2), PEGylated TNF-α, liposomal IL-2, plasmid IL-12 electrogene therapy, oncolytic viruses engineered to express IL-12 or IFN-β, and emerging delivery platforms. Across diverse technological platforms, several pharmacodynamic patterns observed in dogs have also been recapitulated in first-in-human trials, emphasizing the potential wealth of a comparative oncology framework for evaluating novel immunomodulatory strategies. These parallels underscore the value of canine immuno-oncology trials in defining safety and biological activity for engineered cytokine constructs, with direct implications for guiding the development of dose selection and biomarker discovery in the human immuno-oncology field."

First-in-human • IO biomarker • Journal • Review • Brain Cancer • Fibrosarcoma • Glioma • High Grade Glioma • Melanoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Urothelial Cancer • IFNB1 • IL12A • IL2 • TNFA

Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov) - P1/2 | N=51 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Trial completion • Anal Carcinoma • Cervical Cancer • Colorectal Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Penile Cancer • Rectal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Vaginal Cancer • Vulvar Cancer • CD4 • CDKN2A • PD-L1

Study protocol: targeted delivery of interleukin-12 in combination with hepatic artery infusion pump therapy for patients with adrenocortical carcinoma liver metastases. (PubMed, BMC Cancer) - P2 | "For select patients with ACC liver metastasis, HAIP therapy with PDS01ADC may improve disease control and thereby prolong survival."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • IL12A

Short-course (3-month) enzalutamide monotherapy in biochemically recurrent prostate cancer (BCR): Preliminary prostate specific membrane antigen tumor volume (PSMA-TV) data. (ASCO 2026) - P2 | " NCT06096870 is a clinical trial (n = 50) at the NCI randomizing BCR pts to either enza monotherapy or enza + PDS01ADC (IL-12 immunocytokine). This is the first data presented evaluating PSMA-TV changes after enza in BCR without ADT. Despite this small data set, lack of concordance of PSA and PSMA responses should highlight a need to collect more data to better understand the clinical utility of PSMA scans in defining therapeutic response in BCR. It further indicates the need for caution in the use of PSMA imaging presumptively to define therapeutic benefit or lack thereof in clinical practice."

Monotherapy • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IL12A

Immunocytokines based on IL-12 for cancer therapy: Enhancing efficacy and reducing toxicity. (PubMed, Int Rev Cell Mol Biol) - "This has led to clinical trials in which two ICKs, namely huBC1-IL12 and NHS-IL-12 targeting fibronectin extra domain B and DNA/histone complexes, respectively, have been evaluated. These initial trials have shown a high degree of safety, as well as activation of antitumor immune responses in treated patients."

Journal • Review • Oncology • EDB-FN • IL12A • MSLN • PD-1 • PD-L1

A tumor-targeting IL-12 immunocytokine therapy increases peripheral natural killer (NK) cells with phenotypes associated with increased tumor cell lysis in patients with advanced solid tumors (AACR 2026) - P1 | "PDS01ADC increased peripheral NK cells with specific phenotypes that positively associated with tumor cell lysis, with increases in some cases correlating with clinical response. These findings highlight the importance of deep interrogation of the peripheral immunome and demonstrate the role of NK cells in the biologic activity of PDS01ADC. Studies combining PDS01ADC with other agents to synergize with these NK cell changes are warranted."

Clinical • First-in-human • Metastases • Tumor cell • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • GZMB • IL12A • KLRC1 • NKG2D • TIGIT

Peripheral memory T cells with self-renewing properties increase with tumor-targeting IL-12 immunocytokine therapy (IMMUNOLOGY 2026) - P1 | "This is the first report of a cytokine-based therapy increasing peripheral T cell stemness in mice and humans. Increases in peripheral T cell stemness induced by PDS01ADC correlated with disease stabilization and may serve as an indicator of which patients are more likely to benefit from therapy. These data support future studies combining PDS01ADC with other agents to synergize with this increase in T cell stemness."

IO biomarker • Oncology • Solid Tumor • CD4 • CD8 • GZMB • IL12A • PD-1 • TIGIT

PDS Biotech Announces Publication of Positive PDS01ADC Interim Phase 2 Clinical Trial Data from Stage 1 of NCI-led Metastatic Colorectal Cancer (mCRC) Trial (GlobeNewswire) - "Objective response rate by RECIST v1.1: 77.8% (7/9) at six months; in the parallel trial without PDS01ADC, the ORR was 35% (7/20). 24-month survival rate: Approximately 85%; in the parallel study without PDS01ADC, the 2-year survival rate was approximately 40%. Extrahepatic progression-free survival (PFS): median not reached at minimum follow-up of 13.1 months; in the parallel trial without PDS01ADC, the PFS was 8.1 months."

P2 data • pMMR • Colorectal Cancer

Tumor-Targeted IL-12 (PDS01ADC) with Hepatic Artery Infusion Pump Therapy for Colorectal Liver Metastases: Interim Analysis of a Non-randomized Phase II Trial. (PubMed, JCO Oncol Adv) - P2 | "NCT05286814 is a phase II non-randomized trial evaluating subcutaneous PDS01ADC in combination with HAIP floxuridine and systemic chemotherapy (FOLFOX or FOLFIRI) in patients with unresectable microsatellite stable or mismatch repair-proficient colorectal liver metastases previously treated with at least one line of systemic chemotherapy...Addition of PDS01ADC is not detrimental to HAIP therapy and is associated with both systemic and intratumoral immune modulation. Initial results warrant continuation to full enrollment for further evaluation of clinical and scientific endpoints."

Journal • P2 data • Colorectal Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • CD8 • IL12A

Alterations in peripheral T stem-like memory cells in patients with advanced solid tumors treated with tumor-targeting IL-12 therapy [WITHDRAWN] (AACR 2025) - P1 | "This is the first study on effects of tumor-targeting IL-12 therapy on peripheral TSCM in mouse and human. Greater increases in TSCM TCF1+ fractions may have a role in disease control in patients with advanced solid tumors treated with PDS01ADC. Our data highlight a window for lead-in treatment with PDS01ADC, followed by additional immunotherapies to capitalize on this TSCM burst."

Clinical • IO biomarker • Metastases • Oncology • Solid Tumor • BCL2 • CCR7 • CD4 • CD8 • IL12A • TIGIT

The Quadruple Immunotherapy for Colorectal Cancer (QuICC) Trial for Mismatch Repair-Proficient Metastatic Colorectal Cancer. (PubMed, Oncologist) - P2 | "Quadruplet therapy produced one objective response in unselected mCRC patients (n = 20). There were no responses with triplet therapy (n = 12). The role of ICB-based combination immunotherapy in pMMR CRC remains unclear. NCT04491955."

Journal • Mismatch repair • pMMR • Colorectal Cancer • Oncology • Solid Tumor • IL12A • IL15 • MUC1 • TGFB1

A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov) - P1/2 | N=55 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Dec 2025 ➔ Nov 2026

Trial primary completion date • Anal Carcinoma • Cervical Cancer • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Penile Cancer • Small Intestinal Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Vaginal Cancer • Vulvar Cancer • CD4 • PD-L1

Dynamic PD-L1 Regulation Shapes Tumor Immune Escape and Response to Immunotherapy. (PubMed, Cancers (Basel)) - "To investigate this, we adapted an ordinary differential equation model of combination therapy, incorporating the dynamics of the immune checkpoint inhibitor Avelumab and the immunostimulant NHS-muIL12. This work provides a validated mechanistic framework for adaptive resistance in combination immunotherapy. Quantified parameter differences between responder and non-responder phenotypes enable clearer biological interpretation and support the development of predictive tools for optimizing treatment strategies."

IO biomarker • Journal • Oncology

Dynamic PD-L1 Regulation Shapes Tumor Immune Escape and Response to Immunotherapy. (PubMed, bioRxiv) - "To investigate this, we adapted an ordinary differential equation model of combination therapy, incorporating the dynamics of the immune checkpoint inhibitor Avelumab and the immunostimulant NHS-muIL12. Incorporating therapy-dependent, dynamically regulated PD-L1 expression enabled a biologically grounded mechanism to reproduce experimental observations, leading us to formulate PD-L1 tumor expression as a dynamic variable ( ϵ ) and providing a mechanistic basis for both therapeutic synergy and treatment failure. Our results indicate that tumor resistance is linked to dose-dependent upregulation of PD-L1 following NHS-muIL12 treatment, explaining treatment failure, while PD-1/PD-L1 blockade in combination therapy enables effective anti-tumor immune responses."

IO biomarker • Journal • Oncology

Announced Preliminary Results from Colorectal Cancer Cohort of Phase 2 Clinical Trial with PDS01ADC (PDS Biotech Press Release) - "Metastatic colorectal cancer cohort in study led by the National Cancer Institute met high objective response rate bar for continuation of study of at least 6 of 9 confirmed objective responses by RECIST v1.1. This triggered enrollment expansion under the Simon Two-Stage study design."

P2 data • Colorectal Cancer