PCIB reports main results of Amphinex Phase I/II study against multiple cancers

PCI Biotech (PCIB) the Norwegian biopharmaceutical company, reported today the main results of the completed Phase I/II study of the new component Amphinex® in the combination productPC-A11, where Amphinex is used in combination with the cytotoxic agent bleomycin.

The primary objective of this dose escalation study is to assess the maximum tolerated dose of the new component Amphinex®. Secondary objectives include determination of the antitumour effect of the PC-A11 treatment, as well as pharmacokinetics of the Amphinex® component.

A total of 19 patients were treated in the Phase I/II study, 14 in the dose escalation part and 5 additional patients at the selected therapeutic dose. Sixteen patients completed the first efficacy assessment and 11 completed the second efficacy assessment (4 weeks and at least 8 weeks after treatment, respectively). The other patients were withdrawn from the study either due to the need of other treatment (5 patients) or poor general performance status (3 patients).

The primary objective of the Phase I/II study, dose limiting toxicity, was reached at the fourth dose level by the appearance of skin photosensitivity and significant ulceration of normal tissue in the treated areas. Apart from the photosensitivity observed at the fourth dose level, 13 serious adverse events have been recorded. One of these is deemed drug-related by the investigator. Amphinex seems to be well tolerated under conditions of analgesia and anaesthesia, and no unexpected safety concerns have been raised.

Patients with osteosarcoma (1), squamous cell carcinoma (13) of the head & neck, adenocarcinoma of the breast (4) andmalignant skin adnexal tumour (1) have been included. Strong response to treatment was seen in all patients, with complete clinical regression of target tumours in 87.5% (14 of 16) of the patients completing the first assessment and in 72% (8 of 11) of the patients completing the second assessment.

Head and Neck Squamos Cell Carcinoma (HNSCC) is the primary target population for further development of PC-A11, and 13 of the 19 patients in the Phase I/II study were HNSCC. Eleven of these patients completed the first efficacy assessment and 8 completed the second efficacy assessment. Complete clinical regression of target tumours was seen in 90.9% (10 of 11) of the HNSCC patients completing the first assessment and in 87.5% (7 of 8) of the patients completing the second assessment.

The five last patients have been evaluated by magnetic resonance imaging, in addition to the clinical examination and/or ultrasound that were used for the first 14 patients. The treatment areas contain tissue deformations from previous treatments and the imaging results have been difficult to interpret, as it has proven difficult to discriminate between viable tumour and immunological post-treatment effects in these areas. This issue has to be further investigated in the next clinical trial of PC-A11.

Analysis of the pharmacokinetic data indicates that Amphinex® has a half-life in blood of 14 - 21 days. Amphinex® also seems to be present in the skin for a prolonged period, but is barely detectable 3 months after administration. The absence of drug related side effects other than the observed photosensitivity at the highest dose in the study, suggests that the slow kinetics does not impose any major safety concerns.