Scancell: Update On Phase 1/2 Clinical Trial Of SCIB1 In Stage III/IV Melanoma
6/2/2014 10:24:57 AM
2 June 2014 -- Scancell Holdings plc (‘Scancell’ or the ‘Company’), the developer of novel immunotherapies for the treatment of cancer, is pleased to announce further encouraging results from its on-going Phase 1/2 clinical trial in patients with Stage III/IV melanoma treated with the SCIB1 ImmunoBody?. The updated data was presented in a poster at the 2014 American Society of Clinical Oncology (ASCO) meeting in Chicago on Sunday 1 June 2014.
The Phase 1/2 trial is an open label, non-randomised study to determine the safety and tolerability of four dose levels of SCIB1 administered intramuscularly using an electroporation device. While the primary objective of the study is to access safety and tolerability, the secondary objectives are to evaluate cellular immune responses and to assess any tumour response.
• SCIB1 is safe and well-tolerated, with no dose-limiting or grade 4/5 toxicities observed
• Five of 11 patients in Part 1 receiving 2, 4 or 8mg doses have shown evidence of a clinical response
• Part 1 patients receiving 2mg/4mg doses of SCIB1 had 1-year and 2-year survival rates of 100% and 67%, respectively
• All five Part 1 patients receiving 8mg doses of SCIB1 remain alive
• All 14 Part 2 patients with resected tumours are still alive 16-24 months after study entry (median 21 months); only three patients have disease progression
• 24 of 28 (86%) evaluable patients developed melanoma-specific immune responses
• Survival times are highly encouraging; only 2 of 25 patients receiving at least three doses of 2-8mg of SCIB1 have died since the study started in 2010
• Eight patients are currently on long term treatment with SCIB1
Prof Lindy Durrant, Joint CEO of Scancell and Professor of Cancer Immunotherapy at Nottingham University, commented: “As positive and consistent data continues to emerge from this study, our confidence grows that SCIB1 will play an important role in the management of melanoma. While recognizing the limitations of this open label trial, the results nonetheless detail a high rate of immune responders and a strong immune response with a drug that is well-tolerated and safe. The observation of objective clinical responses and apparent prolongation of survival further add to the evidence that SCIB1 has the potential to dramatically extend lives without the burden of serious side effects in this setting.”
Prof Poulam Patel, Chief Investigator for the trial and Professor of Clinical Oncology at the University of Nottingham, added: “The whole field of cancer immunotherapy is undergoing a fundamental transformation. Although checkpoint inhibitors are continuing to deliver clinical results, the long-term benefits are seemingly only apparent in around a third of patients. Taking the brake off T cells with checkpoint inhibitors and pressing the accelerator with active immunotherapies such as SCIB1 may be an effective way of overwhelming the disease and increasing efficacy even further.”
Part 1 higher dose 8mg study interim results (Stage IV disease only)
• All five patients with Stage IV disease remain alive with a median survival time of 11 months from study entry (range 8-12 months)
• One patient in this cohort has shown a pronounced reduction in lung metastases following SCIB1 treatment, meeting the RECIST* criteria for a partial response by Week 9 of treatment and has started continuation treatment. This is the second patient in the study to show an objective clinical response
• A further patient with breast and lung lesions at study entry remained stable for 6 months and is continuing treatment with SCIB1
• Four of the five patients produced an immune response to SCIB1
• Immune responses to the 8mg dose, measured by Elispot, were up to 10-fold higher than those seen in the lower dose 4mg group; high frequencies of melanoma-specific T cells exceeding 2% of total blood lymphocytes were observed
Part 1 lower dose 2mg/4mg study update (Stage III/IV disease)
• The four patients (of six) who were alive at the time of the December 2012 Part 1 report remain alive
• One patient had multiple tumour lesions which disappeared or decreased in size except for one lesion which was resected; the patient, who is still alive, has subsequently developed another lesion which was also resected
• Two further patients have remained disease-free for 18 and 35 months respectively, having required regular treatment and resection of metastases prior to SCIB1 treatment
• Median survival time in Part 1 patients who received at least three treatments with the 2mg/4mg doses of SCIB1 is now 30 months from study entry and 49 months since diagnosis of metastatic disease
• Five of six patients receiving 2mg/4mg doses of SCIB1 produced an immune response
Part 2 study update (Stage III/IV patients with resected tumours)
• All 14 study patients produced an immune response to SCIB1 treatment
• All patients are still alive after being on the study for between 16 and 24 months
• Only three patients have any evidence of disease progression after 4, 14 and 18 months on the study
• Median survival time of all Part 2 patients since initiating treatment is currently 21 months and 26 months since diagnosis of metastatic disease
Based on clinical staging according to the American Joint Committee on Cancer (Balch et al., Journal of Clinical Oncology 2009: 27(36), 6199-206), the 12 patients receiving SCIB1 therapy who had tumour present at study entry fall into the following categories: patients with advanced, visceral stage M1c disease (n=4); patients with disease restricted to M1a (n=1) or M1b (n=6) metastases and one patient with no distant metastases (M0). The other 16 patients all had fully-resected metastatic disease (Stage III or IV prior to surgery).
• Two M1c patients treated with 0.4mg of SCIB1 had rapidly progressing disease and died after 7 months on study - as expected for patients with visceral metastatic disease. The two other M1c patients received at least 4mg doses of SCIB1; one patient died after 13 months and the other is still alive 11 months after study entry
• The single M1a patient received 2mg/4mg doses and is still alive 38 months after study entry. One M1b patient treated with 0.4 mg of SCIB1 died 16 months after study entry. Of the other five M1b patients, one received 4 mg doses and four received 8 mg doses: they all remain alive. The current median survival time for the M1b patients is 12 months from study entry (range 8-28 months)
• Sixteen patients with fully-resected metastatic disease received either 2mg or 4mg doses of SCIB1 and all remain alive with a current median survival of 22 months (range 16-35) from trial entry. The nine Stage III patients have survived for a median of 26 months since their last resection prior to study entry and two patients have experienced a recurrence (22%). The seven Stage IV patients have survived for a median time of 24 months since their last resection prior to study entry, with two patients showing evidence of disease progression 18 and 20 months post-surgery; this compares extremely favourably with a SouthWest Oncology Group prospective study of resection in Stage IV melanoma patients in which the median overall survival (i.e., when 50% of the patients had died) was 21 months and the median recurrence-free survival was 5 months from the time of surgery (Sosman et al., Cancer 2011: 117(20), 4740-46)
• SCIB1 therapy was well tolerated in all patient groups with no reports of serious drug-related side effects
In conclusion, while this is a Phase 1/2 clinical study and patient numbers are relatively small, there is consistent evidence emerging from this trial that Scancell’s SCIB1 ImmunoBody® therapy can produce a reduction in tumour load as well as inducing a powerful immune response in late-stage melanoma patients. When taken together with the apparent delay in disease progression and increasingly extended survival data, these results are highly encouraging and clearly warrant the continued development of SCIB1 ImmunoBody® as a potentially powerful new addition for the treatment of this disease.
* RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments.
For Further Information:
Dr Richard Goodfellow, Joint CEO
Professor Lindy Durrant, Joint CEO Scancell Holdings Plc
Scancell Holdings Plc + 44 (0) 20 3727 1000
Camilla Hume/Stephen Keys Cenkos Securities + 44 (0) 20 7397 8900
Mo Noonan/Simon Conway FTI Consulting + 44 (0) 20 3727 1000
Overview of the Phase 1/2 trial design
Part 1 of this single arm, open label, Phase 1/2 clinical trial, conducted in five UK centres, was a dose-escalation designed to determine the dose for Part 2. Eleven patients, ten with Stage IV and one with Stage III malignant melanoma were given up to five doses of 0.4mg, 2mg or 4mg of SCIB1, delivered by Ichor Medical Systems’ TriGrid™ electroporation delivery device, over a period of six months. One patient in the 0.4mg dose group and one in the 4mg dose group who received only a single dose of SCIB1 were withdrawn from the study due to progressive disease shortly after study entry and were replaced to ensure that at least three patients in each dose cohort could be fully evaluated for immune response. During the course of the study, regulatory approval was granted to increase the SCIB1 dose from 2mg to 4mg in patients in the 2mg cohort, if the treatment was well tolerated. Two patients in this group received two 4mg doses of SCIB1 and one patient received a single 4mg dose. Regulatory approval was subsequently obtained for treating a cohort of patients with 8mg of drug in Part 1; five patients were enrolled. One patient received three 8 mg doses and one patient received four 8 mg doses of SCIB1. One patient received two doses of 4mg followed by three doses of 8mg and the other two patients both received five 8 mg doses of SCIB1.
In Part 2 of the study, 14 patients with resected Stage III/IV melanoma (nine with Stage III and five with Stage IV) entered the study. One patient was only able to tolerate three doses of 2mg and withdrew from the study. Of the remaining patients, 12 received a full 4mg dose of SCIB1 on five occasions over a period of 6 months and one received four doses of 4mg and one dose of 2mg. In the absence of any serious toxicity in the Part 1 8mg cohort, approval was also obtained to further expand Part 2 to dose up to 13 additional patients with 8mg. Recruitment and dosing of these patients is currently on-going.
During the course of the study, regulatory approval was also granted to continue treating eligible patients for a period of up to 5 years from the formal end of the study. During this period patients can receive further doses of SCIB1 every 3-6 months. Two patients in Part 1 (8mg) and six patients in Part 2 (4mg) are currently receiving extended SCIB1 treatment.
Scancell is developing novel immunotherapies for the treatment of cancer based on its ImmunoBody® and Moditope® technology platforms. Scancell’s first ImmunoBody®, SCIB1 is being developed for the treatment of melanoma and is being evaluated in a Phase 1/2 clinical trial. Data from the trial demonstrate that SCIB1 has a marked effect on tumour load, produces a melanoma-specific immune response and highly encouraging survival trend without serious side effects.
Scancell’s ImmunoBody® vaccines target dendritic cells and stimulate both parts of the cellular immune system; the helper cell system where inflammation is stimulated at the tumour site; and the cytotoxic T-lymphocyte or CTL response where immune system cells are primed to recognise and kill specific cells.
Scancell has also identified and patented a series of modified epitopes that stimulate the production of killer CD4 T cells that destroy tumours without toxicity. The Directors believe that the Moditope® platform could play a major role in the development of safe and effective cancer immunotherapies in the future.
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