A Phase I/IIa, Open, Single-Center Clinical Trial Evaluating the Safety and Anti-Tumor Activity of SNK01 (Natural Killer Cells) Administered in Combination With Gemcitabine/Carboplatin or Gemcitabine/Carboplatin/Cetuximab to Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients Who Have Failed Prior Tyrosine Kinase Inhibitor (TKI) Therapy (SNK_ASTER)
Overview
- Phase
- Phase 1
- Intervention
- SNK01 (Super Natural Killer Cells 01)
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- NKMAX Co., Ltd.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Adverse event
- Last Updated
- 4 years ago
Overview
Brief Summary
This clinical trial is a Single-Center, Open, Phase I/IIa Clinical Trial conducted to evaluate the safety and anti-tumor activity of SNK01 and GC +/- Cetuximab administered in combination to Locally advanced or Metastatic Non-small Cell Lung Cancer Patients who have failed prior Tyrosine Kinase Inhibitor (TKI) therapy at least once.
After the start of the clinical trial, the first 3 subjects complete the enrollment in Cohort 1 in serial order and then 3 subjects are enrolled in Cohort 2 in serial order. After this, Cohorts 1, 3 and Cohorts 2, 4 are independently processed and subjects are enrolled in serial order when new cohorts start and/or replacement subjects are required. For the subjects who are additionally enrolled after the DLT evaluation and the MTD is determined in each dose cohort, no DLT evaluation is conducted.
The subjects allotted to each cohort are administered with the SNK01 manufactured from peripheral blood mononuclear cells total 8 times over a period of about 10 weeks. Combined administration of SNK01 starts from the Cycle 2 (Week 4) of Cytotoxic Chemotherapy and SNK01 is administered at an interval of 1 week starting from the day after the administration of Cytotoxic Chemotherapy and/or Cetuximab (Visit 5-1, D23).
When no disease progression is confirmed at EOT (End of Treatment), disease progression is checked until the clinical trial is over. The adverse events which have occurred during the study period are monitored until the date when the investigator judges that no monitoring is required as the symptom has disappeared or there is no further change in the symptom or the 30th day (±3 d) from the latest date of the administration among Gemcitabine, Carboplatin and Cetuximab after the EOT, whichever comes first.
For all the subjects enrolled in the present clinical trial, safety is checked in accordance with CTCAE V5.0 and effectiveness is checked in accordance with RECIST V1.1 through the vital signs, laboratory test, adverse events, etc. during the study period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •histologically or cytologically diagnosed with Locally advanced or Metastatic Non-small Cell Lung Cancer (TNM 8th edition). However, recurrent Non-small Cell Lung Cancer is also allowed.
- •one or more gene mutations among EGFR, ALK, and ROS1
- •TKI treated for EGFR, ALK, or ROS1 gene mutation at least once or whose progressive disease is confirmed during or after completion of the treatment
- •platinum based chemotherapy (excluding Gemcitabine), other chemotherapy or immunotherapy besides TKI treatment before. (Those who have undergone neoadjuvant chemotherapy or adjuvant chemotherapy are also allowed.)
- •remaining toxicity resulting from previous anti-cancer therapy is grade 1 or lower in accordance with CTCAE V5.
- •However, those who suffer from alopecia not lower than grade 2 or neuropathy of grade 2 related to previous platinum based chemotherapy are allowed to be enrolled.
- •voluntarily decided to participate in the present clinical trial and put their signature on a subject's consent form before start of the trial
- •20 years of age or older
- •at least one lesion measurable by RECIST v1.1
- •life expectancy is 3 months or longer
Exclusion Criteria
- •Subjects who fulfill ANY of the following criteria will not be enrolled into the study:
- •have taken a drug for another clinical trial or participated in another clinical trial within 30 days prior to the enrollment
- •have taken Cetuximab to cure Non-Small Cell Lung Cancer
- •a systemic or partial antineoplastic therapy is scheduled during the period of the present study
- •previous treatments meet the following criteria:
- •Those who have undergone systemic Cytotoxic Chemotherapy, administration of a biologic agent, or a surgery within 3 weeks prior to the enrollment date
- •Those who have undergone Breast Radiotherapy of which the radiation exceeds 30 gray (Gy) for treatment of Non-small Cell Lung Cancer within 6 months prior to the enrollment date
- •Those who have undergone Palliative Radiotherapy on the regions to which a lung cancer is metastasized (bone, brain, etc.) within 1 week before the enrollment date
- •Those who have undergone therapy of EGFR TKIs (Gefitinib, Erlotinib, Afatinib, Osimertinib, etc.), ALK TKIs (Crizotinib, Ceretinib, Alectinib, Brigatinib, etc.) and/or ROS1 TKIs (Crizotinib, etc.) within 2 weeks of the enrollment date
- •an anamnesis of a known allergic reaction or a serious allergic reaction to Gemcitabine, Carboplatin, or another platinum containing compound, Cetuximab or a monoclonal antibody
Arms & Interventions
SNK01 (4ⅹ10^9 cells) + GC
Administration of SNK01 4ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks
Intervention: SNK01 (Super Natural Killer Cells 01)
SNK01 (4ⅹ10^9 cells) + GC
Administration of SNK01 4ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks
Intervention: GC
SNK01 (4ⅹ10^9 cells) + GC + Cetuximab
Administration of SNK01 4ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks + Weekly administration of Cetuximab until the disease progresses or unacceptable toxicity develops
Intervention: SNK01 (Super Natural Killer Cells 01)
SNK01 (4ⅹ10^9 cells) + GC + Cetuximab
Administration of SNK01 4ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks + Weekly administration of Cetuximab until the disease progresses or unacceptable toxicity develops
Intervention: GC
SNK01 (4ⅹ10^9 cells) + GC + Cetuximab
Administration of SNK01 4ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks + Weekly administration of Cetuximab until the disease progresses or unacceptable toxicity develops
Intervention: Cetuximab
SNK01 (6ⅹ10^9 cells) + GC
Administration of SNK01 6ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks
Intervention: SNK01 (Super Natural Killer Cells 01)
SNK01 (6ⅹ10^9 cells) + GC
Administration of SNK01 6ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks
Intervention: GC
SNK01 (6ⅹ10^9 cells) + GC + Cetuximab
Administration of SNK01 6ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks + Weekly administration of Cetuximab until the disease progresses or unacceptable toxicity develops
Intervention: SNK01 (Super Natural Killer Cells 01)
SNK01 (6ⅹ10^9 cells) + GC + Cetuximab
Administration of SNK01 6ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks + Weekly administration of Cetuximab until the disease progresses or unacceptable toxicity develops
Intervention: GC
SNK01 (6ⅹ10^9 cells) + GC + Cetuximab
Administration of SNK01 6ⅹ10\^9 cells/dose 8 times at an interval of 1 week + Administration of Cytotoxic Chemotherapy (GC) up to 4 cycles at an interval of 3 weeks + Weekly administration of Cetuximab until the disease progresses or unacceptable toxicity develops
Intervention: Cetuximab
Outcomes
Primary Outcomes
Adverse event
Time Frame: Up to 12 months
Adverse event (AE)
Maximum Tolerated Dose of the dose of SNK01 + GC + (or Cetuximab)
Time Frame: 28 days
Dose-Limiting Toxicity assessment
Secondary Outcomes
- objective response rate(every 12 weeks, up to the time of death or tumor progression, maximum 24 months)
- Progression-free survival(every 12 weeks, up to the time of death or tumor progression, maximum 24 months)
- Disease Control Rate(every 12 weeks, up to the time of death or tumor progression, maximum 24 months)
- Time to progression(every 12 weeks, up to the time of death or tumor progression, maximum 24 months)
- Duration of response(every 12 weeks, up to the time of death or tumor progression, maximum 24 months)
- QoL(every 12 weeks, up to the time of death or tumor progression, maximum 24 months)