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

Study Overview
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Brief Summary
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During this open label study patients will receive IMM-101 in conjunction with a recognised standard of care for metastatic or unresectable cancer for the patient's specific tumour type. The primary objective of the study is to provide safety data for IMM-101 in combination with a number of selected standard of care regimens.

Detailed Description
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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.

Official Title
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A Novel Phase I/IIa Open Label Study of IMM 101 in Combination With Selected Standard of Care (SOC) Regimens in Patients With Metastatic Cancer or Unresectable Cancer at Study Entry

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Biological: IMM-101
* Drug: Gemcitabine
* Drug: Nabpaclitaxel
* Drug: Capecitabine
* Drug: Folinic Acid
* Drug: Fluorouracil
* Drug: Irinotecan
* Drug: Oxaliplatin
* Biological: cetuximab
* Biological: Anti-PD1
* Biological: Ipilimumab
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMM-101 + Gem panc ca<br>IMM-101 will be given in combination with standard gemcitabine monotherapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;|
| Experimental: IMM-101+Gem/nab-paclitaxel panc ca<br>IMM-101 will be given in combination with standard gemcitabine + nab-paclitaxel combination therapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;Drug: Nabpaclitaxel<br>* Standard of Care chemotherapy<br>* Other names: Abraxane;|
| Experimental: IMM-101+Gem+capecitabine panc ca<br>IMM-101 will be given in combination with gemcitabine +capecitabine combination therapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;Drug: Capecitabine<br>* Standard of Care chemotherapy<br>|
| Experimental: IMM-101 + FOLFIRINOX panc ca<br>IMM-101 will be given in combination with standard FOLFIRINOX (FOLinic acid, Fluorouracil, IRINotecan and OXaliplatin) treatment. The treatment regimen with IMM 101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Folinic Acid<br>* Standard of Care chemotherapy<br>* Other names: Leucovorin;Drug: Fluorouracil<br>* Standard of Care chemotherapy<br>* Other names: 5FU;Drug: Irinotecan<br>* Standard of Care chemotherapy<br>* Other names: Camptosar;Drug: Oxaliplatin<br>* Standard of Care chemotherapy<br>* Other names: Eloxatin;|
| Experimental: IMM-101+FOLFOX colorectal cancer<br>IMM-101 will be given in combination with standard FOLFOX (FOLinic acid, Fluorouracil and OXaliplatin) treatment. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Folinic Acid<br>* Standard of Care chemotherapy<br>* Other names: Leucovorin;Drug: Fluorouracil<br>* Standard of Care chemotherapy<br>* Other names: 5FU;Drug: Oxaliplatin<br>* Standard of Care chemotherapy<br>* Other names: Eloxatin;|
| Experimental: IMM-101+FOLFIRI+CETUXIMAB CRC<br>IMM-101 will be given in combination with standard FOLFIRI (FOLinic acid, Fluorouracil and IRInotecan) + cetuximab combination treatment. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Folinic Acid<br>* Standard of Care chemotherapy<br>* Other names: Leucovorin;Drug: Fluorouracil<br>* Standard of Care chemotherapy<br>* Other names: 5FU;Drug: Irinotecan<br>* Standard of Care chemotherapy<br>* Other names: Camptosar;Biological: cetuximab<br>* Standard of Care immunotherapy<br>* Other names: Erbitux;|
| Experimental: IMM-101+Gem cholangio<br>IMM-101 will be given in combination with standard gemcitabine monotherapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;|
| Experimental: IMM-101+Gem lung ca<br>IMM-101 will be given in combination with standard gemcitabine monotherapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;|
| Experimental: IMM-101+Gem + nab-paclitaxel lung ca<br>IMM-101 will be given in combination with standard gemcitabine + nab-paclitaxel combination therapy. The treatment regimen with IMM 101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;Drug: Nabpaclitaxel<br>* Standard of Care chemotherapy<br>* Other names: Abraxane;|
| Experimental: IMM-101+anti-PD1 lung ca<br>IMM-101 will be given in combination with standard treatment with either pembrolizumab or nivolumab. In order to ensure that there are no increased immune-related adverse events (AEs), the first 3 patients entering the anti-PD1 (pembrolizumab or nivolumab) cohort will receive IMM-101 at an increased dosing interval of every 4 weeks. In the absence of safety concerns for these patients after 3 doses of IMM-101, and following a robust safety review, all subsequent patients recruited to this treatment cohort will switch to the standard, more intensive (2-weekly induction dosing) IMM-101 dosing regimen. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Biological: Anti-PD1<br>* Standard of Care immunotherapy<br>* Other names: nivolumab (OPDIVO);|
| Experimental: IMM-101+Gem melanoma<br>IMM-101 will be given in combination with standard gemcitabine monotherapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;|
| Experimental: IMM-101+anti-PD1 melanoma<br>IMM-101 will be given in combination with standard treatment with either pembrolizumab or nivolumab. The first 3 patients entering the anti-PD1 (pembrolizumab or nivolumab) cohort will receive IMM-101 at an increased dosing interval of every 4 weeks. In the absence of safety concerns for these patients after 3 doses of IMM-101, and following a robust safety review, all subsequent patients recruited to this treatment cohort will switch to the standard, more intensive (2-weekly induction dosing) IMM-101 dosing regimen thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Biological: Anti-PD1<br>* Standard of Care immunotherapy<br>* Other names: nivolumab (OPDIVO);|
| Experimental: IMM-101+ anti-CTLA-4 melanoma<br>IMM-101 will be given in combination with standard treatment with ipilimumab. In order to ensure that there are no increased immune-related adverse events (AEs), the first 3 patients entering the ipilimumab cohort will receive IMM-101 at an increased dosing interval of every 4 weeks. In the absence of safety concerns for these patients after 3 doses of IMM-101, and following a robust safety review, all subsequent patients recruited to this treatment cohort will switch to the standard, more intensive (2-weekly induction dosing) IMM-101 dosing regimen thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Biological: Ipilimumab<br>* Standard of Care immunotherapy<br>* Other names: YERVOY;|
| Experimental: IMM-101+Gem breast cancer<br>IMM-101 will be given in combination with standard gemcitabine monotherapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;|
| Experimental: IMM-101+Gem/ nab-paclitaxel breast<br>IMM-101 will be given in combination with standard gemcitabine + nab-paclitaxel combination therapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;Drug: Nabpaclitaxel<br>* Standard of Care chemotherapy<br>* Other names: Abraxane;|
| Experimental: IMM-101 + Gem sarcoma<br>IMM-101 will be given in combination with standard gemcitabine monotherapy. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Gemcitabine<br>* Standard of Care chemotherapy<br>* Other names: GEMZAR;|
| Experimental: IMM-101+cyclophosphamide<br>IMM-101 will be given in combination with low dose cyclophosphamide (300mg/m2 in patients with solid malignancies. The treatment regimen with IMM-101 will be one dose given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter. | Biological: IMM-101<br>* A suspension of heat killed whole cell Mycobacterium obuense NCTC 13365<br>* Other names: Heat killed M. obuense (NCTC) 13365);Drug: Cyclophosphamide<br>* Standard of Care chemotherapy<br>* Other names: cytophosphane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Safety and tolerability will be measured by AEs, Laboratory abnormalities and local injection site reactions. | Initial assessment at Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Safety and tolerability will be measured by AEs, Laboratory abnormalities and local injection site reactions. | Week 28 through study completion (maximum 4.5 years) | 
| Number of participants with treatment-related adverse events when IMM-101 is given in combination with a checkpoint blockade inhibitor | 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 | Initial assessments at Week 12 and Week 28 then through study completion (maximum 4.5 years) | 
| Response to treatment | 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 | Initial assessment at Week 28 then through study completion (maximum 4.5 years) | 
| Overall survival (OS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholangio, Unresectable cancer, pancreatic, melanoma, breast, lung, colorectal, sarcoma