PEP503

BACKGROUND

There are several cancer treatment modalities including surgery, medication, radiation therapy, and others, depending on the site of the tumor, grade, and stage of cancer, and the physical condition of the patients. About 50% of cancer patients receive radiotherapy throughout their cancer treatment. Radiation therapy causes breaks to the double helix of DNA using a high energy beam, which may induce cell death. However, radiation therapy also has notable disadvantages, such as a longer treatment period and unavoidable side effects. Over the past decades, many technologies and methods have been developed to address this, and while they ameliorate some of the drawbacks of traditional radiation therapy, there is much need for further improvement.

In August 2012, PharmaEngine, Inc. and Nanobiotix, S.A. (ENXTPA: NANO) entered into a License and Collaboration Agreement on a nanoparticle radio-enhancer, PEP503 (Hensify®,NBTXR3). In the preclinical studies, PEP503 (NBTXR3) showed the ability in enhancing tumor killing capability of radiation therapy, while spared the damaging side effects to the healthy tissues. PEP503 has received CE Mark approval for the treatment of locally advanced soft tissue sarcoma. The CE Mark approval enables commercialization of PEP503, under the brand name of Hensify®, in 27 European Union countries.

PEP503 (NBTXR3) – MODE OF ACTION

Radiation therapy uses ionizing radiation to generate free radicals and reactive oxygen species (ROS) when it is directed toward the tumor and interacts with water molecules. The free radicals and ROS can then further break the DNA and lead to cell apoptosis.

PEP503 is a nanoparticle formulation of hafnium oxide crystals (HfO2), a radio-enhancer for local treatment. Hafnium oxide represents a high electron density nanomaterial designed to interact with ionizing radiation in order to locally (i.e., where the nanoparticles are) generate energy dose deposit.

When PEP503 is in the tumor cell, due to the high density and atomic number of hafnium, the probability of energy absorption is higher than that of the water molecule. Therefore, PEP503 will generate the same type of effect as water molecules in tumor cell under radiotherapy, but by several orders of magnitude higher.

Clinical Development

PEP503 (Hensify®,NBTXR3) has been designated as a class III medical device by some EU regulatory authorities. Unlike the three clinical phases required for drug approval, the regulatory approval of a medical device requires only the pilot and pivotal studies. In September 2011, PEP503 was granted approval by ANSM, the French regulatory authority (formerly AFSSAPS), to start the phase I clinical trial. A total of 22 patients were recruited in this soft tissue sarcoma study. The first preliminary clinical results were presented at the ASCO annual meeting in May 2015, and the final results were presented at ESTRO in April 2015. With the proof of concept data from the phase I trial, a pivotal study of soft tissue sarcoma was launched in Europe, South Africa, and several Asia Pacific countries. In June 2018, the topline results of the global pivotal study were revealed and showed that PEP503 in combination with radiotherapy met the primary endpoint of pathological Complete Response Rate (pCRR) as compared to radiotherapy alone in patients with locally advanced soft tissue sarcoma of the extremity and trunk wall.

In addition to soft tissue sarcoma, Nanobiotix and PharmaEngine are performing clinical trials in head & neck cancers, liver cancers (liver metastasis and hepatocellular carcinoma), rectal cancer, prostate cancer, as well as in combination with anti-PD1 antibodies in head & neck cancers and non-small cell lung cancer. Under the license and collaboration agreement, PharmaEngine is responsible for the clinical development in the Asia Pacific region.

Market forecast

Nowadays about 50% of cancer patients worldwide receive radiation treatment. In Asia, potential indications for PEP503 include head and neck cancer, oral cavity cancer, rectal cancer, esophageal cancer, brain cancer and hepatocellular carcinoma. There is a niche role for PEP503 in this huge radiotherapy market.

Indications & Stages

  • RESEARCH
  • PRECLINICAL
  • PHASE I
  • PHASE II
  • PHASE III
  • NDA

PEP503Crystalline hafnium oxide

Soft Tissue Sarcoma*
CE MARK
Head & Neck Cancer (RTx alone)**
PHASE I/II TRIAL ONGOING
Liver Cancer (RTx alone)**
PHASE I/II TRIAL ONGOING
Prostate Cancer (RTx alone)**
PHASE II/III TRIAL ONGOING
Head & Neck Cancer (RTx + chemo)
PHASE II/III TRIAL ONGOING
Rectal Cancer (RTx + chemo)
PHASE II/III TRIAL ONGOING
H&N & Lung Cancer (RTx + anti-PD-1/PD-L1)**
IND APPROVED

*Collaboration with Nanobiotix **Nanobiotix clinical study

References

NANOLIPOSOMAL IRINOTECAN WITH FLUOROURACIL AND FOLINIC ACID IN METASTATIC PANCREATIC CANCER AFTER PREVIOUS GEMCITABINE-BASED THERAPY (NAPOLI-1): A GLOBAL, RANDOMISED, OPEN-LABEL, PHASE 3 TRIAL

Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Lancet. 2016; 387: 545-57

MANAGEMENT OF METASTATIC PANCREATIC CANCER: CURRENT TREATMENT OPTIONS AND POTENTIAL NEW THERAPEUTIC TARGETS

Sclafani F, Iyer R, Cunningham D, Starling N; Crit Rev Oncol Hematol. 2015; 95: 318-36

CANCER OF THE PANCREAS: ESMO CLINICAL PRACTICE GUIDELINES FOR DIAGNOSIS, TREATMENT AND FOLLOW-UP

Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goere? D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D; Ann Oncol. 2015; 26 Suppl 5: v56-68

PHASE I STUDY OF NANOLIPOSOMAL IRINOTECAN (PEP02) IN ADVANCED SOLID TUMOR PATIENTS

Chang TC, Shiah HS, Yang CH, Yeh KH, Cheng AL, Shen BN, Wang YW, Yeh CG, Chiang NJ, Chang JY, Chen LT; Cancer Chemother Pharmacol 2015; 75: 579–86

A MULTINATIONAL PHASE II STUDY OF LIPOSOME IRINOTECAN (PEP02) FOR PATIENTS WITH GEMCITABINE-REFRACTORY METASTATIC PANCREATIC CANCER

A. H. Ko, M. A. Tempero, Y. Shan, W. Su, Y. Lin, E. Dito, A. Ong, G. Yeh, L. Chen; Br J Cancer 2013; 109: 920–25

A RANDOMIZED PHASE II STUDY OF PEP02 (MM-398), IRINOTECAN OR DOCETAXEL AS A SECOND-LINE THERAPY IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC GASTRIC OR GASTRO-OESOPHAGEAL JUNCTION ADENOCARCINOMA

Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A; Ann Oncol. 2013; 24: 1567–73

CONVECTION-ENHANCED DELIVERY OF NANOLIPOSOMAL CPT-11 (IRINOTECAN) AND PEGYLATED LIPOSOMAL DOXORUBICIN (DOXIL) IN RODENT INTRACRANIAL BRAIN TUMOR XENOGRAFTS

Krauze MT, Noble CO, Kawaguchi T, Drummond D, Kirpotin DB, Yamashita Y, Kullberg E, Forsayeth J, Park JW, Bankiewicz KS; Neuro Oncol. 2007; 9:393403

PHASE I STUDY OF NBTXR3 NANOPARTICLES, IN PATIENTS WITH ADVANCED SOFT TISSUE SARCOMA (STS)

S. Bonvalot, C.L. Pechoux, T.D. Baere, et al; J Clin Oncol 32:5s, 2014 (suppl; abstr10563)

NEW USE OF METALS AS NANOSIZED RADIOENHANCERS

Pottier A, Borghi E, Levy L; Anticancer Res. 2014 Jan;34(1):443-53. Review

HAFNIUM OXIDE NANOPARTICLES: TOWARD AN IN VITRO PREDICTIVE BIOLOGICAL EFFECT?

Marill J, Anesary NM, Zhang P, Vivet S, Borghi E, Levy L, Pottier A; Radiat Oncol. 2014 Jun 30;9:150

FIRST-IN-HUMAN STUDY TESTING A NEW RADIOENHANCER USING NANOPARTICLES (NBTXR3) ACTIVATED BY RADIATION THERAPY IN PATIENTS WITH LOCALLY ADVANCED SOFT TISSUE SARCOMAS

Bonvalot S, Le Pechoux C, De Baere T, et al; Clin Cancer Res. 2017 Feb 15;23(4):908-917

PACKAGE LEAFLET

BACK TO R & D PIPELINE
Go To Top