IMM-101-007

Immodulon Therapeutics Ltd

6-9 The Square, Stockley Park, Uxbridge, United Kingdom, UB11 1FW

Clinical Trials Administrator, Immodulon Therapeutics Ltd, 0044 020 3137 6346 , info@immodulon.com

Clinical Trials Administrator, Immodulon Therapeutics Ltd, 0044 020 3137 6346 , info@immodulon.com

No

No

No

Final

05 Apr 2016

Yes

09 Sep 2015

Yes

09 Sep 2015

No

The primary objective of this Simon optimal 2-stage design study was to investigate the efficacy of IMM-101 in combination with radiation induced tumour necrosis (induced by CyberKnife treatment) in patients with colorectal cancer with metastatic disease who had received prior chemotherapy. Secondary objectives were: a) to investigate the safety and tolerability of IMM-101 , and b) to conduct an exploratory investigation of selected markers of tumour burden and immunological status. No formal hypothesis was tested and no interim analyses were planned or undertaken. The first scheduled CT scan was at Wk 12 and the primary time point was Wk 24. In similar cohorts of advanced cancer patients with a similar profile of range and number of prior chemotherapies, findings following treatment with Regorafenib, Cetuximab (Grothey et al, 2013), and Panitumumab (van Cutsem, 2007) suggest that ~50% of patients enrolled into this study would have experienced disease progression by Wk 8.

This study was conducted in accordance with the World Medical Association Declaration of Helsinki as amended (Fortaleza, 2013), the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines (CPMP/ICH/135/95), EU Clinical Trial Directive (2001/20/EC), designated standard operating procedures (SOPs), and with local laws and regulations relevant to the use of new therapeutic agents. A Data Monitoring Committee (DMC), consisting of 3 clinicians with relevant general and specialist expertise was established to interpret on an on-going basis the study conduct and results independent of the study conduct. The DMC responsibility was to safeguard the interests of the studies' patients, and potential patients with respect to conduct, safety and tolerability of the study and protect its validity and credibility. The DMC would also adjudicate and confirm any patients who demonstrate stabilisation and/or response to treatment, if applicable.

30 May 2012

No

Yes

United Kingdom: 12

12

12

0

0

0

0

0

0

5

7

0

overall study (overall period)

Not applicable

IMM-101

UPI EMA/569517

Heat killed Mycobacterium obuense NCTC13365

Suspension for injection

Intradermal use

Patients received single 0.1 mL intradermal injections of IMM-101 (10 mg/mL) every 2 weeks for the first three doses, with the second of these doses being on the same day as the SBRT administered by the CyberKnife procedure then following a rest of 4 weeks after the third dose of IMM-101, patients continued to receive IMM-101 every 2 weeks for the next 3 doses followed by a further 4-week treatment-free period. Thereafter IMM-101 was given at 4-week intervals for up to a further 9 months or until patient withdrawal for any reason.

overall study

IMM-101 treated

All analyses were based on the safety population, which comprised all patients who received at least one dose of the investigational medicinal product IMM-101.

IMM-101 treated

IMM-101 treated

All analyses were based on the safety population, which comprised all patients who received at least one dose of the investigational medicinal product IMM-101.

The disease stabilisation rate at 24 weeks defined as the proportion of patients who had complete or partial response or stable disease based on CT scan findings, absence of clinical signs and symptoms of progression, did not withdraw due to disease progression prior to/at the Week 24 assessment and were alive at the Week 24 assessment.

Primary

Week 24

Safety and tolerability criteria defined as no clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles as judged by: • Local and systemic toxicities. • Number, type and degree of toxicities as measured by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.

Secondary

Throughout the study

Disease progression at Week 12 was defined as progressive disease, based on CT scan findings or based on clinical signs and symptoms of progression, withdrawal due to progression at/prior to the Week 12 assessment or death by Week 12.

Secondary

Week 12

Overall survival was calculated as the date of death minus the date of Day 0 + 1, and was expressed in months.

Secondary

Overall survival incorporated both on study deaths and deaths post withdrawal.

Throughout the entire study duration.

Adverse event data were collected from study entry until patient completion, withdrawal or death and for IMP-related AEs, for 30 days after the last study visit. AEs leading to death due to disease progression were reported as AEs, not SAEs. AEs with first onset or worsening after first administration of IMP were summarised descriptively.

17

Safety population