Date: 2016-01-11
Type of information: Interim results
phase: 1-2
Announcement: interim results
Company: Scancell Holdings (UK)
Product: DNA ImmunoBody® vaccine SCIB1
Action
mechanism: plasmid/immunotherapy product. SCIB1 is a plasmid DNA which encodes a human antibody molecule engineered to express a melanoma antigen called Tyrosinase-Related Protein 2 (TRP2) plus two helper T cell epitopes. Following immunisation, the engineered antibody will be expressed and be taken up by dendritic cells, resulting in the development of immune responses against tumour cells expressing the TRP2 antigen. SCIB1 was designed so that the Fc component of the engineered antibody will be recognised by the high affinity CD64 receptor present on dendritic cells, leading to a significant enhancement of both the frequency and avidity of the T cell immune response. The induction of high avidity T cells against TRP-2 is expected to lead to the inhibition and regression of both primary and metastatic tumour growth.
Disease: Stage III/IV malignant melanoma
Therapeutic area: Cancer - Oncology
Country: UK
Trial
details: The study is an investigation of a novel immunotherapy, SCIB1, for the treatment of melanoma. SCIB1 is a solution of plasmid DNA molecules which will express a modified antibody in human cells. The antibody modifications are designed to stimulate the patient's immune T cells to have a strong and specific reaction against melanoma cells which should then be eliminated. SCIB1 is injected into muscle using a device which simultaneously delivers an electrical impulse to enhance the transfer of SCIB1 into muscle cells. The trial will assess the safety and tolerability of SCIB1, the safety and performance of the injection device and the immunological effects of SCIB1. This is the first study of SCIB1 in humans and the trial has two parts, in the first part the dose will be escalated to determine a safe and tolerable level up to a maximum of 8 mg per dose. In the second part patients will receive the dose determined in the first part. Patients will have stage III or IV melanoma, be HLA type A2 and have a life expectancy of at least three months. All patients will receive 5 injections of SCIB1 over 5.5 months. At the discretion of the investigator, patients may continue to receive SCIB1 at 3-6 month intervals for 5 years. The study will be conducted at major cancer centres in the UK only and is expected to last for seven years. Patients will be followed up for five years after they have completed the trial. (NCT01138410)
Latest
news: * On January 11, 2016, Scancell and ImmunID released data showing patient immunologic response to cancer vaccine SCIB1 can be demonstrated through monitoring changes in the diversity of T cells found in the blood. The data was generated through a pilot study performed in conjunction with Scancell’s Phase 1/2 trial of the SCIB1 cancer vaccine in patients with resected stage III/IV metastatic melanoma. ImmunID’s ImmunTraCkeR® assay was used to assess T cell diversity in the blood from patients before and during treatment with SCIB1. Results showed variations in T cell diversity kinetics during SCIB1 treatment, underlining the immune-modulatory effect of the vaccine, and indicated that patients had developed an immunological response to SCIB1. Data also suggested that patients who relapsed did not have an adequate immunological response to the vaccine. These preliminary results will be confirmed in a larger patient population through an extended collaboration between Scancell and ImmunID. * On July 9, 2015, Scancell announced that it has closed patient recruitment for its SCIB1 ImmunoBody® Phase 1/2 clinical trial in patients with Stage III/IV melanoma. The Phase 1/2 clinical trial, conducted across five UK centres, is an open label, non-randomised study to determine the safety and tolerability of SCIB1 administered intramuscularly using an electroporation device (TriGrid Delivery System, manufactured by Ichor Medical Systems, USA). Part 1 was a dose-escalation designed trial to determine the dose for Part 2. While the primary objective of the study is to access safety and tolerability, the study is also assessing immune response and anti-tumour activity, and the ability of SCIB1 to delay or prevent disease recurrence in patients with resected disease. In total, 35 patients have now been treated with SCIB1, including ten patients at the higher 8mg dose. Six patients remain on long-term treatment and have received between one and nine additional 4mg or 8mg doses of SCIB1 every three to six months. * On June 2, 2015, Scancell announced further results from its on-going Phase 1/2 clinical trial of SCIB1, its DNA ImmunoBody being developed for the treatment of patients with melanoma. Updated data on patients with resected Stage III or Stage IV melanoma was presented in a poster at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on Monday 1 June 2015. The poster entitled: “A clinical trial of SCIB1, a DNA vaccine that targets dendritic cells in vivo, in fully resected melanoma patients: a vaccine to prevent recurrence” by PM Patel et al, demonstrates that the latest clinical data on patients with fully resected tumours is highly promising, and suggests that SCIB1 may uniquely offer protection from recurrence of melanoma with little associated toxicities. The poster summarises current data from a subset of patients in the trial with resected tumours. 16 patients with fully resected Stage III (n=9) or Stage IV (n=7) melanoma were immunised with 4mg of SCIB1 by intramuscular electroporation at 3-weekly intervals, then subsequently at three and six months. Patients tolerating treatment were allowed to continue treatment for up to five further years. Immune responses were assayed by proliferation and Elispot assays. All 16 patients with resected disease (two in Part 1 and 14 in Part 2) are still alive. Survival times are very encouraging: median survival time for Stage III patients (n=9) and Stage IV patients (n=7) is 34 and 31 months, respectively. Only five patients (31%) have had a recurrence of the disease; all other patients have been disease-free for between 27 and 46 months since study entry* (median follow-up of 34 months). The median for disease-free survival and overall survival (when 50% of patients have progressed or died, respectively) have therefore not yet been reached. All 16 patients showed melanoma-specific immune responses. All patients who continued treatment showed strong T cell memory responses following three monthly boosts with SCIB1. SCIB1 was safe and well-tolerated, with no grade 4/5 toxicities observed other than those related to disease progression and one case of pneumonia. Prof Lindy Durrant, Joint CEO of Scancell and Professor of Cancer Immunotherapy at Nottingham University, commented: “We are excited to report this latest clinical data on melanoma patients with fully resected tumours. The on-going positive results from this Phase 1/2 trial gives us confidence that our SCIB1 ImmunoBody? has the potential to become the first non-toxic effective adjuvant treatment for resected melanoma. All 16 participants in this part of the study remain alive, suggesting that SCIB1 may offer protection from tumour recurrence in these patients. Data to date demonstrates that SCIB1 is safe and well-tolerated, and the very encouraging survival times suggest a strategy of using SCIB1 in such resected melanoma patients to extend their lives.” * On May 18, 2015, Scancell announced that the latest data from the ongoing Phase 1/2 clinical trial of SCIB1, its DNA ImmunoBody® being developed for the treatment of patients with melanoma, will be presented in a poster at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, May 29 - June 2, 2015. An abstract of the poster can be accessed through the ASCO website. The summary of the results contained therein relates to data available at the time of abstract submission. A further update on clinical outcomes, including survival time, will be given as part of the poster presentation. * On January 12, 2015, Scancell Holdings announced that Joint CEOs Dr Richard Goodfellow and Professor Lindy Durrant will be making corporate presentations 12-15 January 2015, coincident with JP Morgan’s 33rd Annual Healthcare Conference, San Francisco, CA, USA. An update on clinical outcomes in the Company’s on-going Phase 1/2 clinical trial in patients with Stage III/IV melanoma treated with the SCIB1 ImmunoBody® will be given as part of these presentations. It will be reported that the overall median survival of Part 1 patients with tumour present at trial entry and who received at least three doses of 2-8mg of SCIB1 is 24 months. This compares favourably with first line untreated Stage IV disease where patients with no visceral disease had a median survival of 11 months and patients with visceral disease had a median survival of six months (Sosman et al., 2011 Cancer 117:4740-4706). The status of the patients with resected tumours at study entry is equally promising. The 14 patients in Part 2 of the trial have been on study for 23-32 months (median 28 months) and only three have evidence of disease progression. Of particular note, all resected patients (n=16; two from Part 1 and 14 from Part 2) are still alive and only four have progressed. The median recurrence-free survival (when 50% of patients have died) has not been reached; these resected patients have a median survival time of 30 months for Stage III patients (n=9) and 27 months for Stage IV patients (n=7). This compares very favourably with reported data from a peptide vaccine trial following two years of treatment, in which 50% of Stage III patients had disease progression and 19% had died; while 52% of Stage IV patients had disease progression and 33% had died (Slingluff et al., 2011 J Clin Oncol 29:2924-2932). * On October 14, 2014, Scancell Holdings provided a research and development update following the Company’s AGM. To date, 32 patients have been treated with SCIB1, including seven at the higher 8mg dose. Six patients are currently on long-term treatment and have received between 4 and 6 further doses of SCIB1 every 3-6 months. Although recruitment of patients with advanced disease remains challenging it is expected that enrolment for the study will be completed during 2Q15. A new clinical centre has been established at the Royal Surrey County Hospital in Guildford to accelerate recruitment. SCIB1 continues to be a safe and well tolerated treatment with no withdrawals from the study due to adverse events. Overall, only five of the 27 patients who have received at least three doses of 2-8mg SCIB1 since commencement of the study in 2010 have died. Median survival time in Part 1 patients who received at least three treatments with the 2mg/4mg doses of SCIB1 is now 34 months since study entry. This group of patients had 1-year, 2-year and 3-year survival rates of 100%, 67% and 50%, respectively. For the Part 1 8mg cohort of patients, who were recruited later, the median survival time is currently 13 months since study entry. The median survival time since initiating treatment with SCIB1 in Part 2 patients with resected disease (and receiving 4mg doses of SCIB1) is currently 25 months. Importantly, all 16 patients (two in Part 1 and 14 in Part 2) with fully-resected metastatic disease (nine Stage III and seven Stage IV) are still alive with a median survival time of 26 months since study entry (range 20-39 months) and only four have shown evidence of disease progression. The Stage III patients have a median survival time of 26 months since study entry and two (22%) have progressed. This compares extremely favourably with results from a peptide vaccine trial (Slingluff et al., 2011) where 52% of fully-resected Stage III patients had progressed and 33% had died twoyears after the start of treatment. The Stage IV patients treated with SCIB1 have a median survival time of 24 months since study entry and two of these patients (22%) have also progressed. In the Slingluff study, 50% of the fully-resected Stage IV patients had progressed and 19% had died after two years of treatment. These results in patients with resected disease suggest that SCIB1 may have an important role to play as first line treatment in adjuvant melanoma. These are patients who no longer have measurable disease (following surgery) and are often generally quite well. However, they are at a high risk of recurrence and currently have very few, if any, effective treatment options. This represents a significant and as yet untapped market opportunity, including some 360,000 patients in the US alone, of whom around 45% have the MHC antigen HLA-A2 and are therefore suitable for SCIB1 treatment. Animal data supporting the synergistic effect of combining SCIB1 with PD-1 blockade was announced in August. Any patients that progress following SCIB1 monotherapy, or indeed any patient with more advanced disease, may therefore benefit from the combination of SCIB1 with acheckpoint inhibitor. * On June 2, 2014, Scancell announced further 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. 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 Overall survival: 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) Safety • 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. * On March 21, 2014, Scancell Holdings has announced completion of patient dosing with 8mg of SCIB1 ImmunoBody® (‘SCIB1’) in Part 1 of its on-going Phase 1/2 clinical trial in patients with Stage III/IV melanoma. Following preliminary evidence from Part 1 of the study showing that a 4mg dose of SCIB1 produced an immune response that might be associated with clinical benefit in patients with malignant melanoma, regulatory approval was obtained for treating a cohort of up to six patients with a higher, 8mg dose of SCIB1. Five patients with metastatic tumour present have been recruited and dosed, with no reported drug or device-related serious adverse events. Immunology and clinical responses in this higher dose cohort of patients are currently being analysed and will be reported by the end of Q2 2014. Regulatory approval to expand Part 2 of the study to include up to 13 patients receiving the 8mg dose was obtained in October 2013. With the absence of any serious toxicity in the 8mg Part 1 cohort, enrolment into this cohort has now been closed and new patients will be now be recruited into the expanded 8mg Part 2 cohort. The first such patient was dosed with SCIB1 earlier this week. Scancell looks forward to reporting the results from Part 1 of the study later this year. * On December 9, 2013, Scancell Holdings has announced results from Part 2 of its on-going Phase 1/2 clinical trial in patients with Stage III/IV melanoma treated with the SCIB1 ImmunoBody as well as an update from patients in Part 1 of the study. Part 2 study results: All 14 study patients produced a melanoma-specific T-cell response to treatment. All patients are still alive; only three patients have any evidence of disease progression. Median survival time of Part 2 patients since initiating treatment is currently 15 months; 21 months since diagnosis of metastatic disease. Six patients are continuing on extended, long-term treatment with SCIB1. One patient in the 0.4mg cohort, all three patients in the 2mg/4mg dose cohort and two patients in the 4mg dose cohort mounted a measurable proliferation response to the melanoma-specific epitopes in SCIB1. In addition, the patient with the differential clinical response was assessed using the ELISPOT assay and made a strong response to the melanoma TRP-2 antigen. SCIB1 therapy was well tolerated with no reports of serious drug-related side effects in line with results reported from Part 1 of the study Part 1 study update: The four patients who were alive at the time of the initial Part 1 report (December 2012) remain alive. Median survival time in Part 1 patients who received at least three treatments with the 2mg/4mg doses of SCIB1 is now 25 months. All 14 patients responded to treatment in either the proliferation or ELISPOT assay. Twelve patients were immune responders in the proliferation assay, 13 patients responded in the ELISPOT assay and 11 patients responded in both assays, including the patient who only received three doses of 2mg of SCIB1. Broad, high frequency responses were seen against both the two CD8+ T cell epitopes and against the two CD4+ T cell epitopes. Six patients responded to all four epitopes, five patients responded to three epitopes and three patients responded to two epitopes. Statistically significant responses (p>0.0001) were seen after three, four or five immunisations but not after two, indicating that at least three doses are required for a strong immune response to develop. These results confirm that Scancell’s SCIB1 ImmunoBody therapy is producing a melanoma-specific immune response in patients with Stage III/IV melanoma. This is particularly evident in patients with resected disease. Together with the immunological and clinical data from Part 1 of the study, the results suggest that these induced immune responses might also be contributing to the control of tumour in these patients. Due to these encouraging results six patients are continuing on extended, long-term treatment with SCIB1. * On December 6, 2012, Scancell Holdings has announced preliminary results from Part 1 of the Phase 1/2 clinical trial of its DNA ImmunoBody® vaccine in patients with Stage III/IV malignant melanoma. Of the six patients allocated to the 2mg and 4mg dose cohorts and who received at least four doses of SCIB1, four have shown a vaccine-induced T cell response to treatment. Although the study was not designed primarily to measure tumour response, one patient in the 4mg dose cohort with multiple tumour lesions at study entry had a differential response to treatment including partial or complete regression of all lung metastases. A further two patients who had all their tumours surgically removed prior to SCIB1 treatment have remained disease-free more than a year after first dosing. The vaccine produced very few side effects, none of which were serious. Three of the four patients in the 4mg cohort are still alive and one remains disease-free more than a year after starting treatment. The fourth patient progressed and died too soon after first dosing for any effect to be seen. Two out of the three patients in the 2/4mg cohort are still alive and one remains disease-free more than a year after starting treatment. The third patient died of progressive disease after 63 weeks. Three out of four patients in the 0.4mg dose group have died. The fourth patient is still alive 27 months after starting treatment. One patient in the 4mg dose group had a long history of metastatic disease and multiple tumour lesions present at the start of treatment (including several in her lungs), all of which decreased in size or disappeared completely following six months of treatment with SCIB1 except for one abdominal tumour nodule which increased in size and which will be resected. This \"differential response\" pattern is typical of immunotherapeutic agents and is the first signal that SCIB1 may be having an impact on the course of the disease as well as inducing an immune response. Two further patients on SCIB1 remain disease-free more than one year after treatment started. The first patient had a history of gradual disease progression in the six months prior to study entry, including the development of multiple tumour nodules, which were excised prior to study treatment. This patient was dosed five times with 4mg SCIB1 and had no tumour present at study entry so could not be evaluated for tumour response but is still disease-free 15 months after first dosing and 18 months after the last tumour surgery. The second patient (in the 2/4mg cohort), who also received two 4mg doses at three and six months after the start of dosing, was entered into the study after all recurrent tumour had been resected and remains disease-free, 17 months after first dosing and 23 months after the last tumour excision. Whilst these results are promising it should be emphasised that they will have to be confirmed in larger, controlled studies in due course. All three patients in the 2/4mg dose cohort and one patient in the 4mg dose cohort produced an immune response to the melanoma specific epitopes in SCIB1. Only one of the patients in the lowest dose group showed any immune response to treatment. Immune response was measured by peptide-specific proliferation that was at least twice the background control at each time point and at least twice the pre-treatment control value on two or more of the six time points measured. The patient with the differential clinical response was also assessed using a cultured enzyme-linked immunosorbent (ELISPOT) assay and made a strong response to the melanoma TRP-2 antigen. These preliminary results suggest that therapeutic vaccination with SCIB1 induces specific immune responses that may lead to clinical benefit. In view of the positive results and minimal side effects seen with the 4mg dose the Company intends to evaluate an 8mg dose in a further cohort of three to six patients with evaluable disease, thereby permitting an assessment of the safety and immunogenicity of an increased dose of SCIB1 in addition to the effect of this higher dose on tumour burden. This additional cohort will be evaluated in parallel with the second part of the Phase 1/2 study which is primarily designed to assess the effect of the 4mg dose on immune response in patients who have had all tumour removed prior to treatment.
As with previously reported data, SCIB1 continues to be a safe and well tolerated treatment with no withdrawals from the study due to drug-related adverse events. All 20 patients with resected disease remain alive including the four patients on the 8mg dose. The median survival time in the 16 patients with resected disease who received 2-4 mg doses of SCIB1 is now 35 months.
The last patient in the formal six month study will be dosed in October this year after which the Company will analyse the data and prepare a clinical study report. Patients on long-term continuation treatment will continue to be dosed for up to five years from the start of their treatment regime.
