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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 4
- 主要终点
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Have adequate bone marrow, hepatic and renal function
排除标准
- •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.
研究组 & 干预措施
IMM-101 + Gem panc ca
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.
干预措施: IMM-101 (Biological)
IMM-101 + Gem panc ca
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.
干预措施: Gemcitabine (Drug)
IMM-101+Gem/nab-paclitaxel panc ca
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.
干预措施: IMM-101 (Biological)
IMM-101+Gem/nab-paclitaxel panc ca
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.
干预措施: Gemcitabine (Drug)
IMM-101+Gem/nab-paclitaxel panc ca
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.
干预措施: Nab-paclitaxel (Drug)
IMM-101+Gem+capecitabine panc ca
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.
干预措施: IMM-101 (Biological)
IMM-101+Gem+capecitabine panc ca
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.
干预措施: Gemcitabine (Drug)
IMM-101+Gem+capecitabine panc ca
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.
干预措施: Capecitabine (Drug)
IMM-101 + FOLFIRINOX panc ca
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.
干预措施: IMM-101 (Biological)
IMM-101 + FOLFIRINOX panc ca
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.
干预措施: Folinic Acid (Drug)
IMM-101 + FOLFIRINOX panc ca
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.
干预措施: Fluorouracil (Drug)
IMM-101 + FOLFIRINOX panc ca
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.
干预措施: Irinotecan (Drug)
IMM-101 + FOLFIRINOX panc ca
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.
干预措施: Oxaliplatin (Drug)
IMM-101+FOLFOX colorectal cancer (CRC)
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.
干预措施: IMM-101 (Biological)
IMM-101+FOLFOX colorectal cancer (CRC)
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.
干预措施: Folinic Acid (Drug)
IMM-101+FOLFOX colorectal cancer (CRC)
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.
干预措施: Fluorouracil (Drug)
IMM-101+FOLFOX colorectal cancer (CRC)
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.
干预措施: Oxaliplatin (Drug)
IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC)
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.
干预措施: IMM-101 (Biological)
IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC)
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.
干预措施: Folinic Acid (Drug)
IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC)
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.
干预措施: Fluorouracil (Drug)
IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC)
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.
干预措施: Irinotecan (Drug)
IMM-101+FOLFIRI+CETUXIMAB colorectal cancer (CRC)
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.
干预措施: cetuximab (Biological)
IMM-101+Gem cholangio
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.
干预措施: IMM-101 (Biological)
IMM-101+Gem cholangio
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.
干预措施: Gemcitabine (Drug)
IMM-101+Gem lung ca
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
干预措施: IMM-101 (Biological)
IMM-101+Gem lung ca
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
干预措施: Gemcitabine (Drug)
IMM-101+Gem + nab-paclitaxel lung ca
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.
干预措施: IMM-101 (Biological)
IMM-101+Gem + nab-paclitaxel lung ca
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.
干预措施: Gemcitabine (Drug)
IMM-101+Gem + nab-paclitaxel lung ca
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.
干预措施: Nab-paclitaxel (Drug)
IMM-101+ anti-programmed death-1 (PD1) lung ca
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.
干预措施: IMM-101 (Biological)
IMM-101+ anti-programmed death-1 (PD1) lung ca
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.
干预措施: Anti-PD1 (Biological)
IMM-101+Gem melanoma
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.
干预措施: IMM-101 (Biological)
IMM-101+Gem melanoma
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.
干预措施: Gemcitabine (Drug)
IMM-101+ anti-programmed death-1 (PD1) melanoma
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.
干预措施: IMM-101 (Biological)
IMM-101+ anti-programmed death-1 (PD1) melanoma
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.
干预措施: Anti-PD1 (Biological)
IMM-101+ anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) melanoma
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.
干预措施: IMM-101 (Biological)
IMM-101+ anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) melanoma
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.
干预措施: Ipilimumab (Biological)
IMM-101+Gem breast cancer
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.
干预措施: IMM-101 (Biological)
IMM-101+Gem breast cancer
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.
干预措施: Gemcitabine (Drug)
IMM-101+Gem/ nab-paclitaxel breast
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.
干预措施: IMM-101 (Biological)
IMM-101+Gem/ nab-paclitaxel breast
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.
干预措施: Gemcitabine (Drug)
IMM-101+Gem/ nab-paclitaxel breast
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.
干预措施: Nab-paclitaxel (Drug)
IMM-101 + Gem sarcoma
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.
干预措施: IMM-101 (Biological)
IMM-101 + Gem sarcoma
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.
干预措施: Gemcitabine (Drug)
IMM-101+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.
干预措施: IMM-101 (Biological)
IMM-101+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.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
时间窗: 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.
次要结局
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0(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(From screening until study termination an average of 3 months.)
- 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)
- 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.)