Study of IMM 101 in Combination With Standard of Care in Patients With Metastatic or Unresectable Cancer
Phase 1
Terminated
- Conditions
- Metastatic Cancer
- Interventions
- Registration Number
- NCT03009058
- Lead Sponsor
- Immodulon Therapeutics Ltd
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IMM-101 + Gem panc ca IMM-101 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. IMM-101 + Gem panc ca Gemcitabine 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. IMM-101+Gem/nab-paclitaxel panc ca Nab-paclitaxel 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. IMM-101+Gem/nab-paclitaxel panc ca Gemcitabine 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. IMM-101+Gem+capecitabine panc ca Gemcitabine 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. IMM-101+Gem+capecitabine panc ca Capecitabine 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. IMM-101 + FOLFIRINOX panc ca Folinic Acid 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. IMM-101 + FOLFIRINOX panc ca Fluorouracil 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. IMM-101 + FOLFIRINOX panc ca Irinotecan 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. IMM-101 + FOLFIRINOX panc ca Oxaliplatin 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. IMM-101+FOLFOX colorectal cancer (CRC) Folinic Acid 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. IMM-101+FOLFOX colorectal cancer (CRC) Fluorouracil 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. IMM-101+FOLFOX colorectal cancer (CRC) Oxaliplatin 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. IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC) Folinic Acid 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. IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC) Fluorouracil 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. IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC) Irinotecan 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. IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC) cetuximab 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. IMM-101+Gem cholangio Gemcitabine 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. IMM-101+Gem lung ca Gemcitabine 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 IMM-101+Gem + nab-paclitaxel lung ca Gemcitabine 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. IMM-101+Gem + nab-paclitaxel lung ca Nab-paclitaxel 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. IMM-101+Gem melanoma Gemcitabine 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. IMM-101+ anti-programmed death-1 (PD1) lung ca Anti-PD1 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. IMM-101 + Gem sarcoma Gemcitabine 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. IMM-101+ anti-programmed death-1 (PD1) melanoma Anti-PD1 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. IMM-101+ anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) melanoma Ipilimumab 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. IMM-101+Gem breast cancer Gemcitabine 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. IMM-101+Gem/ nab-paclitaxel breast Gemcitabine 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. IMM-101+Gem/ nab-paclitaxel breast Nab-paclitaxel 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. IMM-101+cyclophosphamide IMM-101 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. IMM-101+cyclophosphamide Cyclophosphamide 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. IMM-101+Gem+capecitabine panc ca IMM-101 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. IMM-101+FOLFOX colorectal cancer (CRC) IMM-101 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. IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC) IMM-101 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. IMM-101+Gem cholangio IMM-101 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. IMM-101+Gem lung ca IMM-101 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 IMM-101+ anti-programmed death-1 (PD1) lung ca IMM-101 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. IMM-101+Gem melanoma IMM-101 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. IMM-101+ anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) melanoma IMM-101 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. IMM-101+Gem breast cancer IMM-101 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. IMM-101+Gem/ nab-paclitaxel breast IMM-101 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. IMM-101+Gem/nab-paclitaxel panc ca IMM-101 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. IMM-101 + FOLFIRINOX panc ca IMM-101 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. IMM-101+Gem + nab-paclitaxel lung ca IMM-101 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. IMM-101+ anti-programmed death-1 (PD1) melanoma IMM-101 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. IMM-101 + Gem sarcoma IMM-101 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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).
Trial Locations
- Locations (4)
Centre Léon Bérard, Dpt Medecine & INSERM
🇫🇷Lyon, France
Gustave Roussy Cancer Center
🇫🇷Villejuif, France
St George's University of London, Institute of Infection and Immunity
🇬🇧London, United Kingdom
Royal Marsden Hospital Foundation Trust
🇬🇧London, United Kingdom