Study of IMM 101 in Combination With Standard of Care in Patients With Metastatic or Unresectable Cancer

The study will consist of three phases - Screening, Treatment and Maintenance. Patients who provide informed consent, will participate in a Screening period of up to 28 days to establish eligibility. Once eligibility is confirmed, patients will enter the Treatment Phase of the study.

In the Treatment Phase all patients will receive IMM-101 for 28 weeks.

At Week 32, if the Investigator considers it in the patients' best interest patients will progress to the Maintenance Phase of the study and will continue to be dosed every 4 weeks (or as close to this interval as permitted due to practical or logistical considerations). Patients will be followed up for assessment of safety, response to treatment, survival, and immunological markers for up to 4.5 years.

• IMM-101 (Biological), also known as Heat killed M. obuense (NCTC 13365): A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365
• Gemcitabine (Drug), also known as GEMZAR: Standard of Care chemotherapy
• Nab-paclitaxel (Drug), also known as Abraxane: Standard of Care chemotherapy
• Capecitabine (Drug), also known as Xeloda: Standard of Care chemotherapy
• Folinic Acid (Drug), also known as Leucovorin: Standard of Care chemotherapy
• Fluorouracil (Drug), also known as 5FU: Standard of Care chemotherapy
• Irinotecan (Drug), also known as Campto, Camptosar: Standard of Care chemotherapy
• Oxaliplatin (Drug), also known as Eloxatin: Standard of Care chemotherapy
• cetuximab (Biological), also known as Erbitux: Standard of Care immunotherapy
• Anti-PD1 (Biological), also known as pembrolizumab (KEYTRUDA),, nivolumab (OPDIVO): Standard of Care immunotherapy
• Ipilimumab (Biological), also known as YERVOY: Standard of Care immunotherapy
• Cyclophosphamide (Drug), also known as cytophosphane: Standard of Care chemotherapy

Primary outcomes

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [Due to the early termination of the study the outcome measure timeframe was until study termination, an average of 3 months.]: Safety and tolerability will be measured by incidence and severity of adverse events (AEs), Laboratory abnormalities and local injection site reactions.

Secondary outcomes

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [Week 28 through study completion (maximum 4.5 years)]: Safety and tolerability will be measured by AEs, Laboratory abnormalities and local injection site reactions.
• Number of Participants With Treatment-related Adverse Events When IMM-101 is Given in Combination With a Checkpoint Blockade Inhibitor [From screening until study termination an average of 3 months.]: Safety and tolerability will be measured by AEs, Laboratory abnormalities and local injection site reactions to evaluate whether there is any exacerbation of toxicity normally observed with these agents
• Response to Treatment [Per protocol the initial assessment was at Week 28 then through study completion (maximum 4.5 years). Due to early termination of the study, response to treatment was measured at Week 11 for both patients]: Response to treatment, (defined as immune related Stable Disease (irSD), immune related Partial Response (irPR) and immune related Complete Response (irCR) as assessed by the Investigator: * Immune-related Complete Response (irCR) is the disappearance of all lesions, measured or unmeasured, and no new lesions * Immune-related Partial Response (irPR) is a ≥50% drop in tumour burden from baseline as defined by the irRC * Immune-related Progressive Disease (irPD) is ≥25% increase in tumour burden from the lowest level recorded. * Everything else is considered immune-related Stable Disease (irSD).
• Overall Survival (OS) [From date of randomization until date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.]: Assessment of overall survival (defined as the time from enrolment to death due to any cause).

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Metastatic or unresectable cancer and considered by their physician to be indicated for a new line of SOC as listed in the protocol
* Are ineligible for a disease specific clinical study with IMM-101
* Have an estimated life expectancy greater than 3 months (from Day 0)
* Give signed informed consent for participation in the study
* Have an Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) Performance Status of ≤2 at Day 0.
* Have adequate bone marrow, hepatic and renal function

Exclusion Criteria:

* Patient has previously received treatment with IMM-101
* Patient is currently part way through a course of chemotherapy or immunotherapy
* Patient is receiving concomitant treatment with another investigational product
* Patient has received an investigational drug within the 4 weeks prior to IMM 101 administration
* Patient has significant cardiovascular disease
* Patient has any previous or concurrent malignancy (excluding adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin and/or non melanoma skin cancer, or if previous malignancy was more than 5 years prior to Screening and there are no signs of recurrence)
* Patient has co existing active infection or medical condition which will substantially increase the risk associated with the patient's participation in the study
* Patient has uncontrolled hypercalcaemia
* Patient has previously experienced an allergic reaction to any mycobacterial product.
* The patient has a history of non-infectious pneumonitis that required steroids or current pneumonitis
* Patient has received live vaccine within 30 days of planned start of study medication
* Patient is pregnant or a breast feeding woman.
* Patient is unwilling to use a medically acceptable, effective method of contraception throughout the treatment period and for at least 6 months after discontinuation of treatment.
* Patient has used depot corticosteroids in the 6 weeks before initiation of Screening
* Patient has had chronic use of systemic corticosteroids within the 2 week period before the first administration of IMM-101
* Patient has received a blood transfusion within 4 weeks prior to Screening
* In the opinion of the Investigator, the patient is unable or unwilling to comply with the protocol.

Participant flow

Outcome results

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Primary), Count of participants, Participants: IMM-101 in Combination With Anti PDL1 in Melanoma 1
• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Secondary)
• Number of Participants With Treatment-related Adverse Events When IMM-101 is Given in Combination With a Checkpoint Blockade Inhibitor (Secondary), Count of participants, Participants: IMM-101 in Combination With Anti PDL1 in Melanoma 1
• Response to Treatment (Secondary), Count of participants, Participants: IMM-101 in Combination With Anti PDL1 in Melanoma 1
• Overall Survival (OS) (Secondary), Count of participants, Participants: IMM-101 in Combination With Anti PDL1 in Melanoma 0

Adverse events

Time frame: Adverse events were collected from the time of consent until 28(±7 days) received at week 10 date which is around 3 months after the last dose of IMM-101. Serious Adverse Events were followed to resolution irrespective of the date of the last dose

Other adverse events by term

Limitations and caveats: Only two patients were enrolled into the study before the study was terminated early by the Sponsor for commercial reasons. There were no specific safety concerns based on the data from the two patients treated. These limited data provide some preliminary indication regarding the safety and tolerability of IMM-101 when administered in combination with nivolumab. No meaningful assessment of efficacy could be made given that only two patients were enrolled into the study.

• Study Protocol (PDF, 2016-10-25)
• Statistical Analysis Plan (PDF, 2017-09-26)

• David Cunningham, MD FRCP, Principal investigator, Royal Marsden Hospital Foundation Trust

NIH grants: 2016