A Phase 1/2 Safety Study of Intratumourally Dosed INT230-6

Official Title

A Phase 1/2 Safety Study of Intratumourally Administered INT230-6 in Adult Subjects With Advanced Refractory Cancers

Summary:

This study evaluates the intratumoural administration of escalating doses of a novel, experimental drug, INT230-6. The study is being conducted in patients with several types of refractory cancers including those at the surface of the skin (melanoma, head and neck, lymphoma, breast) and tumours within the body such (pancreatic, colon, liver, lung, etc.). Sponsor also plans to test INT230-6 in combination with anti-PD-1 antibodies.

Trial Description

Primary Outcome:

• Rate and severity of treatment-emergent adverse events ≥ grade 3 attributed to study drug using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5)

Secondary Outcome:

• Preliminary Efficacy: Control or Regression of Injected Tumours by Measurement of Length, Width and Height (in centimeters) Radio-graphically Using Computer Tomography or Magnetic Resonance Imaging to Calculate Tumour Volumes (cubic centimeters) Over Time.
• Determine pharmacokinetic parameter Peak Plasma (Cmax in ng/mL) of each of the 3 main components of INT230-6.
• Determine key pharmacokinetic parameter, Area Under the Curve (AUC) (ng*hr/mL) of each of the 3 main components of INT230-6.
• Key pharmacokinetic parameters, half live (hours) of each of the 3 main components of INT230-6.

INT230-6 is comprised of a 3 agents in a fixed ratio - a cell permeation enhancer and two, potent anti-cancer payloads (cisplatin and vinblastine sulfate). The penetration enhancer facilitates dispersion of the two drugs throughout injected tumours and enables increased diffusion into cancer cells. (Nonclinical safety studies showed no findings following drug injection into healthy tissues.)

Historically physicians administer the two active drugs comprising INT230-6 by intravenous (IV) infusion to achieve a systemic blood level at the limit of tolerability. The objective is destroy both visible tumours and unseen circulating cancer cells (micro-metastases). Unfortunately, dosing drugs IV delivers only a small amount with a low concentration at the tumour site. This approach especially for late stage cancers is not highly effective and often quite toxic to the patient.

Attempts at direct intratumoural injection with chemotherapeutic agents have not shown the ability to treat the injected tumour, non-injected tumours or micro-metastases. This lack of efficacy for local administration is due possibly to poor dispersion and a lack of cell uptake of the agents.

Due to the use of the novel cell penetration enhancing agent INT230-6 treatment demonstrates strong efficacy in animals having large tumours. The Sponsor's in vivo, non-clinical data shows that INT230-6 thoroughly saturates and kills injected tumours. In addition, the drug induces an adaptive (T-cell mediated) immune response that attacks not only the injected tumour, but non-injected tumours and unseen micro-metastases. Cured animals become permanently immunized against the type of cancer that INT230-6 eliminates.

Clinical trial IT-01 will thus seek to determine the safety and potential efficacy of dosing INT230-6 directly into several different types of cancers. In addition animal studies showed a strong synergy of INT230-6 with immune modulation agents. Thus as part of study IT-01 the Sponsor will seek to understand the safety and efficacy of INT230-6 when administered in combination with immuno-therapeutic agents such as antibodies that target Programmed Cell Death (PD-1 or anti-PD-1) receptors.

This study seeks to understand whether tumour regression can be achieved and patient outcomes improved.

View this trial on ClinicalTrials.gov