A first study designed evaluate docetaxel, the current standard-of-care chemotherapy (SOC), in combination with PDS0301*, a novel antibody-drug conjugate or ADC, in patients diagnosed with metastatic castration sensitive (mCSPC) and castration resistant (mCRPC) prostate cancer, has shown a decrease in prostate specific antigen (PSA) levels in all patients participating in the clinical study.

The data from the  first-in-human phase 1 / 2 study, to be presented by National Cancer Institute as an oral presentation by Ravi A. Madan, MD, Head, Prostate Cancer Clinical Research Section, Genitourinary Malignancies Branch, Center for Cancer Research of the National Cancer Institute, an Institute of the National Institutes of Health, at the 11th International Cytokine and Interferon Society (Cytokines 2023) meeting, being held October 15 to 18, 2023 in Athens, Greece, further show that the combination was well-tolerated at all tested dose levels.

The study evaluates PDS0301, a novel investigational tumor-targeting, antibody-conjugated Interleukin 12 (Il-12), being developed by PDS Biotechnology in combination with SOC chemotherapy.

The investigational drug, formerly known as M9241 and NHS-IL12, was studied in a novel triple combination at the National Cancer Institute in a Phase 2 trial (NCT04287868) in combination with PDS0101, a HPV16-targeted immunotherapy, and bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β)RII receptor (a TGF-β ‘trap’) fused to a human IgG1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1).

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The triple combination was studied in checkpoint inhibitor (CPI)-naïve and -refractory patients with advanced HPV-positive anal, cervical, head and neck, vaginal, and vulvar cancers who have failed prior therapy.

Proliferation, potency and longevity
IL-12 is a well-documented T cell stimulating cytokine, which can enhance growth and function of T cells.[1][2]

The novel ADC enhances the proliferation, potency and longevity of T cells and natural killer (NK) cells in the tumor microenvironment. PDS0301 is given by subcutaneous injection and is designed to improve the safety profile of IL-12 and to enhance the anti-tumor response.

“We are encouraged by the preliminary data from the Phase 1/2 clinical trial evaluating PDS0301 in combination with docetaxel for patients with metastatic prostate cancer which has the potential to improve treatment outcomes for patients with advanced and refractory prostate cancers that have spread to other parts of the body,” noted Lauren V. Wood, MD, Chief Medical Officer of PDS Biotechnology.

“The results of this study could provide insight into the potential use of PDS0301 with chemotherapy across multiple solid tumors,” Wood added.

Study design
In this study, eighteen patients (11 with mCSPC and 7 with mCRPC) with a median age of 69 years (range 39-82) were evaluated for clinical activity and toxicity. Three dose levels of PDS0301 (8.0 mcg/kg, 12.0 mcg/kg, and 16.8 mcg/kg) in combination with docetaxel (75 mg/m2) were administered every three weeks beginning with the second cycle of treatment. The dose-limiting toxicity (DLT) window spanned the 6 weeks after initiating docetaxel. While all doses of PDS0301 were well-tolerated, the 12.0 mcg/kg dose of PDS0301 with chemotherapy provided the best combination of immune response and tolerability.

Interim data highlights to be presented at Cytokines 2023 include:

  • Decrease in PSA levels was seen in all patients at all three tested doses of PDS0301 and ranged from -4% to -100%.
  • All doses of the combination were well-tolerated with one patient experiencing Grade 4 neutropenia.
  • Administration of the combination was associated with decreases in T reg cells and increases in activated natural killer (NK) cells, memory CD8 T cells, proliferating CD4 and CD8 T cells and cytokines INF-γ and Interleukin 10 (IL-10).
  • The changes in immune responses with the combination were independent of the PDS0301 dose.

“The interim data show that adding PDS0301 to docetaxel was associated with increases in peripheral activated natural killer cells, central memory CD8, proliferating CD4 and CD8 cells in addition to cytokines interferon-gamma and Interleukin 10 as well as decreases in T regulatory cells,” explained Frank Bedu-Addo, PhD, President and Chief Executive Officer of PDS Biotech.

“As the first clinical study to evaluate docetaxel and an immunocytokine, we were pleased to see that the combination can be administered every 3 weeks and look forward to its continued evaluation and impact on clinical outcomes for the treatment of metastatic prostate cancer,” Bedu-Addo concluded.


Abstract Title: Combining an IL-12-based Immunocytokine (PDS0301) with Docetaxel in Metastatic Prostate Cancer: Preliminary Safety and Immune Data
Paper Number: 249
Presenting Author: Head, Prostate Cancer Clinical Research Section, Ravi A. Madan
Authors: Renee Donahue, Yo-Ting Tsai, Mohammad O. Atiq, Elias Chandran, Luke Meininger, Fatima Karzai, Marijo Bilusic, Jennifer Marte, Philip M. Arlen, Lisa Cordes, Megan Hausler, Amy Hankin, Nikki Williams, William D. Figg, Jeff Schlom, James L. Gulley, Ravi A. Madan
Session Details: Plenary 3: Cytokines in Cancer Immunity and Immunotherapy, Mittwoch; Olympia A+B
Session Date and Time: October 18, 2023, 10:00-10:15

Note: * In late 2022 PDS Biotechnology signed an agreement with Merck KGaA, Darmstadt, Germany for an exclusive license to M9241 (now known as PDS0301 and formerly known as NHS-IL12). Under the term of the agreement, PDS Biotechnology will assume responsibility for future development, commercialization, and manufacturing of the investigational agent. Also, as part of the agreement, Merck KGaA, received an upfront cash payment of US $5 million and will be entitled to up to US $11 million in development and regulatory milestone payments including first commercial sales for the first 2 indications, and up to US $105 million in commercial milestones, and a 10% royalty on future sales of M9241 with standard step-down provisions. Merck KGaA also received 378,787 shares of PDS Biotechnology’s common stock having a value of US $5 million.

Clinical trials
Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies – ClinicalTrials.gov ID NCT04287868
Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies – ClinicalTrials.gov ID NCT04235777
M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer – ClinicalTrials.gov ID NCT04633252
T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine M9241 in Localized High- and Intermediate-Risk Prostate Cancer Treated With Androgen Deprivation Therapy – ClinicalTrials.gov ID NCT05361798

[1] Franks SE, Santiago-Sanchez GS, Fabian KP, Solocinski K, Chariou PL, Hamilton DH, Kowalczyk JT, Padget MR, Gameiro SR, Schlom J, Hodge JW. Exploiting docetaxel-induced tumor cell necrosis with tumor targeted delivery of IL-12. Cancer Immunol Immunother. 2023 Aug;72(8):2783-2797. doi: 10.1007/s00262-023-03459-7. Epub 2023 May 11. PMID: 37166485; PMCID: PMC10361896.
[2] Strauss J, Deville JL, Sznol M, Ravaud A, Maruzzo M, Pachynski RK, Gourdin TS, Maio M, Dirix L, Schlom J, Donahue RN, Tsai YT, Wang X, Vugmeyster Y, Beier F, Seebeck J, Schroeder A, Chennoufi S, Gulley JL. First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma. J Immunother Cancer. 2023 May;11(5):e005813. doi: 10.1136/jitc-2022-005813. PMID: 37236636; PMCID: PMC10230972.

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