PDS01ADC / EMD Serono, PDS Biotech - 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

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

Early changes in serum proteomic profiles predict anti-tumor activity in patients with advanced HPV-associated malignancies treated with novel combination immunotherapy (SITC 2025) - P1/2 | "Background We previously reported on the clinical activity of an HPV16 cancer vaccine (PDS0101), a tumor-targeting IL-12 immunocytokine (NHS-IL12, PDS01ADC), and a bifunctional agent targeting PD-L1 and TGF-β (bintrafusp alfa, BA) for the treatment of advanced HPV-associated malignancies, which demonstrated promising clinical activity (NCT04287868).1 Here, we perform a comprehensive survey of the peripheral immunome from patients treated with this novel immunotherapeutic combination to query systemic immunological changes and build models predicting clinical response.Methods Peripheral blood was serially collected from patients (n=50) for HPV16 circulating tumor DNA (ctDNA) detection, qualitative serum proteome profiling with the Olink ImmunoOncology platform, and immunophenotyping by flow cytometry. These data pave the way for outcome prediction in patients with HPV-associated malignancies using readily quantifiable molecular correlates from peripheral blood and..."

Clinical • Metastases • Oncology • GZMB • HMOX1 • IFNG • IL12A • IL6 • TGFB1

A tumor-targeting IL-12 immunocytokine therapy in patients with advanced solid tumors increases peripheral natural killer (NK) cells with phenotypes associated with increased tumor cell lysis (SITC 2025) - P1 | "Further studies combining PDS01ADC with other treatments to synergize with these NK cell changes are warranted.Ethics Approval All subjects gave written informed consent. Study protocol (NCT01417546) was approved by the NIH's IRB, and conducted in accordance with institutional and federal guidelines."

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

Increases in peripheral memory T cells with self-renewing properties in patients with advanced solid tumors treated with tumor-targeting IL-12 immunocytokine therapy (SITC 2025) - P1 | "Further studies combining PDS01ADC with other immunotherapies to synergize with this peripheral burst of T cell stemness are warranted.Ethics Approval All subjects gave written informed consent. Study protocol (NCT01417546) was approved by the NIH's IRB, and conducted in accordance with institutional and federal guidelines."

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

New Clinical and Translational Data on PDS Biotechnology’s Novel Investigational Cancer Therapies PDS0101 and PDS01ADC to be Presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire)

Clinical data • Solid Tumor

NHS-IL12 Monotherapy and in Combination With M7824 in Advanced Kaposi Sarcoma (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Sep 2025 ➔ Dec 2028

Monotherapy • Trial primary completion date • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor • CD4 • IL12A

Increased peripheral T stem cell-like memory features in patients with advanced solid tumors treated with tumor-targeting IL-12 immunocytokine therapy. (PubMed, Clin Cancer Res) - "PDS01ADC treatment in patients with advanced solid tumors boosts peripheral T cells with stem-like characteristics, correlating with disease stabilization. Further studies combining PDS01ADC with other immunotherapies to synergize with this peripheral burst of T cell stemness are warranted."

IO biomarker • Journal • Oncology • Solid Tumor • CD4 • CD8 • GZMB • IL12A • PD-1 • TCF7 • TIGIT

PDS Biotech Announces Colorectal Cancer Cohort of Phase 2 Clinical Trial with PDS01ADC Met Criteria for Expansion to Stage 2 Following Positive Stage 1 Results (GlobeNewswire) - P2 | N=70 | NCT05286814 | "PDS Biotechnology Corporation...announced patient recruitment has been completed in Stage 1 of a clinical trial of the Company’s PDS01ADC therapeutic administered systemically in combination with floxuridine (FUDR) administered by hepatic artery infusion pump (HAIP) for patients with metastatic colorectal cancer....The study met the pre-set RECIST v1.1 criteria for expansion into Stage 2 of the study....For the colorectal cancer cohort, if at least 6 of 9 participants experienced an objective response by RECIST v1.1 criteria, the cohort would continue to enroll up to a total of 22 participants. This milestone has been achieved for the colorectal cancer cohort, and enrollment has progressed to Stage 2. The cholangiocarcinoma and adrenocortical cancer cohorts continue to enroll in Stage 1....'We...anticipate completion of patient recruitment for the metastatic colorectal cancer cohort of the study by the fourth quarter of 2025'."

Enrollment status • P2 data • Colorectal Cancer

Combination of HDAC inhibition and cytokine enhances therapeutic HPV vaccine therapy. (PubMed, J Immunother Cancer) - "Together, these findings provide a rationale for the combination of HPV vaccine, NHS-IL12, and Entinostat in the clinical setting for patients with HPV16-associated malignancies."

IO biomarker • Journal • Head and Neck Cancer • 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

PDS Biotech Announces PDS01ADC Clinical Data to be Presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 (GlobeNewswire) - "PDS Biotechnology Corporation...announced that an abstract submitted by the National Cancer Institute ('NCI') reporting clinical data on PDS01ADC, the Company’s IL-12 fused antibody drug conjugate, has been accepted for presentation at the American Association for Cancer Research ('AACR') Annual Meeting 2025..."

Clinical data • Solid Tumor

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) | Recruiting ➔ Active, not recruiting | N=107 ➔ 55

Enrollment change • Enrollment closed • 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

PDS Biotech Announces FDA Clearance of IND Application for Combination of Versamune MUC1 and PDS01ADC to Treat Metastatic Colorectal Cancer (GlobeNewswire) - "PDS Biotechnology Corporation...announced that the U.S. Food and Drug Administration has cleared its Investigational New Drug ('IND') application filed in January 2025 to evaluate a combination of Versamune MUC1 (formerly PDS0103), its novel investigational MUC1-targeted immunotherapy candidate + PDS01ADC to treat MUC1-positive unresectable, metastatic colorectal carcinoma ('mCRC') in patients who failed previous treatment....The National Cancer Institute ('NCI'), under its Cooperative Research and Development Agreement ('CRADA') with PDS Biotech, will lead the Phase 1/2 clinical trial evaluating the combination of Versamune MUC1 + PDS01ADC in recurrent/metastatic colorectal cancer."

IND • New P1/2 trial • Colorectal Cancer

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

21-C-0001: M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=86 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • 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=100 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Dec 2027 | Trial primary completion date: Dec 2024 ➔ Dec 2027

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urology • Urothelial Cancer • CD4