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Study of SO-C101 and SO-C101 in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT04234113
Recruitment Status : Recruiting
First Posted : January 21, 2020
Last Update Posted : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
Sotio a.s.

Tracking Information
First Submitted Date  ICMJE November 14, 2019
First Posted Date  ICMJE January 21, 2020
Last Update Posted Date November 5, 2020
Actual Study Start Date  ICMJE June 13, 2019
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2020)
  • Part A;Number of Participants With Dose-Limiting Toxicities (DLT): [ Time Frame: Through Cycle 1 (a cycle is 21 days] ]
    DLT was defined as any of the following AEs occurring in the first cycle of treatment which were attributable to the study drug: •Grade 5 events not clearly related to disease progression or any other causes, grade 3 or higher non-hematologic toxicity regardless of duration, and Hy's law cases will be considered DLTs. .•Grade 3 AST, ALT, or bilirubinemia that lasts >5 days •Grade 4 neutropenia or thrombocytopenia lasting >7 days
    • Febrile neutropenia
    • Grade 3 or higher thrombocytopenia with bleeding
    • Grade 4 immune-related AEs regardless of duration
    • Grade 3 or grade 4 non-infectious pneumonitis regardless of duration
    • Grade 3 immune-related AEs, excluding colitis, hepatitis, and pneumonitis, that do not downgrade to grade ≤2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids or downgrade to grade 1 or baseline within 14 days
    • Grade 2 pneumonitis that does not resolve to grade 1 within 3 days of care
    • Grade 3 colitis
  • Part A;Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Cycle 1, Day 1 (each cycle is 21 days) through study completion an average of 1 year ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 90 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
  • Part A;Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs [ Time Frame: assessed in average of 7 months ]
    An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 90 days after last dose that were absent before treatment or that worsened relative to pre-treatment state
  • Part A;Number of Participants With Adverse Events (AEs) According to Severity of Grade 3 or Higher Severity Based on NCI CTCAE Version 5.0 [ Time Frame: assessed in average of 7 months ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were graded according to the Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA) as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE. Participants were counted once according to the maximum grade observed
  • Part A;Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 5.0: Biochemistry and Hematology [ Time Frame: Cycle 1 Day 1 (each cycle is 21 days) through study completion, an average of 1 year ]
    Laboratory parameters included hematological and biochemistry includes Na, Cl, ALT, AST, bilirubin (direct, total), alkaline phosphatase, lactate dehydrogenase, creatinine, glucose (preferably fasting) for hyper- or hypoglycemia, urea or blood urea nitrogen, cholesterol, triglyceride, CRP, uric acid, amylase, and lipase, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. Hematology parameters included anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets and white blood cells Hematology panel will include hemoglobin, glycated hemoglobin HbA1c at study entry, hematocrit, red blood cell count (for anemia), reticulocytes, WBC count (with full differentiation for leukopenia, neutropenia and etc)), ALC (lymphopenia), and platelet count assessment of for thrombocytopenia.
  • Part A;Number of Participants With Laboratory Test Abnormalities: Urinalysis [ Time Frame: Cycle 1 Day 1, (each cycle is 21 days) through study completion, an average of 1 year ]
    Urinalysis parameter includes: pH, glucose, protein, bilirubin, urobilinogen. Microscopic examination: red blood cell count, WBC, epithelial cells, bacteria. In case of proteinuria ≥100 mg/dL at screening, a 24-hour urine analysis will have to be performed (prior to the start of SO-C101 treatment) to document 24-hour proteinuria levels and a urine test will continue during the treatment period. In case of increase of proteinuria with ≥300 mg/dL (at any time), a 24-hour urine analysis will be performed. Test abnormalities was defined as deviation from normal range: Urine blood/hemoglobin abnormality was defined as presence and absence of blood/hemoglobin in urine of participants
  • Part A;Number of Participants With Clinically Significant Change From Screening in Vital Signs [ Time Frame: Screening, through study completion, an average of 1 year ]
    Vital signs included blood pressure, pulse rate, respiratory rate and weight. Change from screening values which are considered to be clinically significant based on investigator's judgement
  • Part A; Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score [ Time Frame: Screening, through study completion, an average of 1 year ]
    ECOG performance status was used to assess how disease affect the daily living abilities of a participant. It was measured on a scale ranging from 0 to 4, where 0=fully active (able to carry on all pre-disease activities without restriction); 1=restricted in physically strenuous activity but ambulatory (able to carry out light/sedentary work); 2=ambulatory and capable of all self-care but unable to carry out any work activities (for more than 50% of waking hours); 3=capable of limited self-care, confined to bed or chair (for >50% of waking hours); 4=completely disabled, not capable of any self-care, totally confined to bed or chair. Higher scores signified =more functional impairment of a participant.
  • Part B: Number of Participants With Dose-Limiting Toxicities (DLT): Dose Finding Phase [ Time Frame: Cycle 1 Day 1 to Cycle 2 Day 1 21 days ]
    DLT was defined as any of the following AEs occurring in the first cycle of treatment which were attributable to the study drug: •Grade 5 events not clearly related to disease progression or any other causes, grade 3 or higher non-hematologic toxicity regardless of duration, and Hy's law cases will be considered DLTs. .•Grade 3 AST, ALT, or bilirubinemia that lasts >5 days •Grade 4 neutropenia or thrombocytopenia lasting >7 days
    • Febrile neutropenia
    • Grade 3 or higher thrombocytopenia with bleeding
    • Grade 4 immune-related AEs regardless of duration
    • Grade 3 or grade 4 non-infectious pneumonitis regardless of duration
    • Grade 3 immune-related AEs, excluding colitis, hepatitis, and pneumonitis, that do not downgrade to grade ≤2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids or downgrade to grade 1 or baseline within 14 days
    • Grade 2 pneumonitis that does not resolve to grade 1 within 3 days of care
    • Grade 3 colitis
  • Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events [ Time Frame: Cycle 1 Day 1, up to 90 days after last dose of study drug (assessed in average of 7 months ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 90 days after last dose that were absent before treatment or that worsened relative to pre-treatment state
  • Part B: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events [ Time Frame: Cycle 1 Day 1, up to 90 days after last dose of study drug (assessed in average of 7 months ]
    An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 90 days after last dose that were absent before treatment or that worsened relative to pre-treatment state
  • Part B: Number of Participants With Adverse Events (AEs) According to Severity of Grade 3 or Higher Severity Based on NCI CTCAE Version 5.0 [ Time Frame: Cycle 1 Day 1, (each cycle is 21 days) through study completion, an average of 1 year ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were graded according to the Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA) as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE. Participants were counted once according to the maximum grade observed.
  • Part B: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 5.0: Biochemistry and Hematology [ Time Frame: Cycle 1 Day 1, (each cycle is 21 days) through study completion, an average of 1 year ]
    Laboratory parameters included hematological and biochemistry parameters. Biochemistry parameters includes Na, Cl, ALT, AST, bilirubin (direct, total), alkaline phosphatase, lactate dehydrogenase, creatinine, glucose (preferably fasting) for hyper- or hypoglycemia, urea or blood urea nitrogen, cholesterol, triglyceride, CRP, uric acid, amylase, and lipase, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. Hematology parameters included anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets and white blood cells Hematology panel includes hemoglobin, glycated hemoglobin HbA1c at study entry, hematocrit, red blood cell count (for anemia), reticulocytes, WBC count (with full differentiation for leukopenia, neutropenia and etc)), ALC (lymphopenia), and platelet count assessment of for thrombocytopenia.
  • Part B: Number of Participants With Laboratory Test Abnormalities: Urinalysis [ Time Frame: Screening, through study completion, an average of 1 year ]
    Urinalysis parameter includes: pH, glucose, protein, bilirubin, urobilinogen. Microscopic examination: red blood cell count, WBC, epithelial cells, bacteria. In case of proteinuria ≥100 mg/dL at screening, a 24-hour urine analysis will have to be performed (prior to the start of SO-C101 treatment) to document 24-hour proteinuria levels and a urine test will continue during the treatment period. In case of increase of proteinuria with ≥300 mg/dL (at any time), a 24-hour urine analysis will be performed. Test abnormalities was defined as deviation from normal range: Urine blood/hemoglobin abnormality was defined as presence and absence of blood/hemoglobin in urine of participants
  • Part B: Number of Participants With Clinically Significant Change From Screening in Vital Signs [ Time Frame: Screening, through study completion, an average of 1 year ]
    Vital signs included blood pressure, pulse rate, respiratory rate and weight. Change from screening values which are considered to be clinically significant based on investigator's judgement.
  • Part B: Number of Participants With Eastern Cooperative Oncology Group [ECOG] [ Time Frame: Screening, through study completion, an average of 1 year ]
    ECOG performance status was used to assess how disease affect the daily living abilities of a participant. It was measured on a scale ranging from 0 to 4, where 0=fully active (able to carry on all pre-disease activities without restriction); 1=restricted in physically strenuous activity but ambulatory (able to carry out light/sedentary work); 2=ambulatory and capable of all self-care but unable to carry out any work activities (for more than 50% of waking hours); 3=capable of limited self-care, confined to bed or chair (for >50% of waking hours); 4=completely disabled, not capable of any self-care, totally confined to bed or chair. Higher scores signified =more functional impairment of a participant.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2020)
  • Part A PK parameters [ Time Frame: assessed in average of 2 months ]
    Assess plasma concentration of SO-C101 at various timepoints
  • Part A Objective response rate (ORR) [ Time Frame: assessed in average of 5 months ]
    based on investigator review of radiographic images according to iRECIST
  • Part A Best overall response (BOR) [ Time Frame: assessed in average of 5 months ]
    BOR by iRECIST
  • Part A Duration of Response (DOR) [ Time Frame: assessed in average of 5 months ]
    DOR by iRECIST
  • Part A Clinical benefit rate (CBR) [ Time Frame: assessed in average of 5 months ]
    CBR by iRECIST
  • Part A Progression-Free Survival (PFS) [ Time Frame: assessed in average of 5 months ]
    PFS by iRECIST
  • Part A Immunogenicity analysis to assess antibodies to SO-C101 in human serum [ Time Frame: assessed in average of 4 months ]
    to assess antibodies to SO-C101 in human serum
  • Part B PK parameters of SO-C101 administered in combination with pemrolizumab [ Time Frame: assessed in average of 2 months ]
    Assess plasma concentration of SO-C101 (administered in combination with pembrolizumab) at various timepoints
  • Part B Objective response rate (ORR) [ Time Frame: assessed in average of 5 months ]
    SO-C101combined with pemrolizumab based on investigator review of radiographic images according to iRECIST
  • Part B Best overall response (BOR) of SO-C101 [ Time Frame: assessed in average of 5 months ]
    combined with pemrolizumab by iRECIST
  • Part B Duration of Response (DOR) [ Time Frame: assessed in average of 5 months ]
    of SO-C101 combined with pembrolizumab by iRECIST
  • Part B Clinical benefit rate (CBR) [ Time Frame: assessed in average of 5 months ]
    of SO-C101 combined with by iRECIST
  • Part B Progression-Free Survival (PFS) [ Time Frame: assessed in average of 5 months ]
    of SO-C101combined with pemrolizumab by iRECIST
  • Immunogenicity analysis to assess antibodies to SO-C101 [ Time Frame: assessed in average of 4 months ]
    SO-C101 in human serum
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of SO-C101 and SO-C101 in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors
Official Title  ICMJE A Multicenter Open-label Phase 1/1b Study to Evaluate the Safety and Preliminary Efficacy of SO-C101 as Monotherapy and in Combination With Pembrolizumab in Patients With Selected Advanced/Metastatic Solid Tumors
Brief Summary A multicenter open-label phase 1/1b study to evaluate the safety and preliminary efficacy of SO-C101 as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors
Detailed Description This study will assess the safety and tolerability of SO-C101 administered as monotherapy and in combination with an anti-PD-1 antibody (pembrolizumab) in patients with selected relapsed/refractory advanced/metastatic solid tumors (renal cell carcinoma, non-small cell lung cancer, small-cell lung cancer, bladder cancer, melanoma, Merkel-cell carcinoma, skin squamous-cell carcinoma, microsatellite instability high solid tumors, triple-negative breast cancer, mesothelioma, thyroid cancer, thymic cancer, cervical cancer, biliary track cancer, hepatocellular carcinoma, ovarian cancer, gastric cancer, head and neck squamous-cell carcinoma, and anal cancer).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Thyroid
  • Renal Cell Carcinoma
  • Non Small Cell Lung Cancer
  • Small-cell Lung Cancer
  • Bladder Cancer
  • Melanoma
  • Merkel Cell Carcinoma
  • Skin Squamous Cell Carcinoma
  • Microsatellite Instability High
  • Triple Negative Breast Cancer
  • Mesothelioma
  • Thymic Cancer
  • Cervical Cancer
  • Biliary Tract Cancer
  • Hepatocellular Carcinoma
  • Ovarian Cancer
  • Gastric Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Anal Cancer
Intervention  ICMJE
  • Drug: SO-C101
    SO-C101
  • Drug: pembrolizumab
    pembrolizumab
Study Arms  ICMJE
  • Experimental: Experimental: Part A (SO-C101 Monotherapy)
    Drug: SO-C101
    Intervention: Drug: SO-C101
  • Experimental: Experimental: Part B (SO-C101 combined with pembrolizumab)
    Drug: SO-C101 Drug: pembrolizumab
    Interventions:
    • Drug: SO-C101
    • Drug: pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 15, 2020)
96
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with selected histologically or cytologically confirmed advanced and/or metastatic solid tumors who are refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
  • ECOG performance score 0-1. Patients with ECOG is 2 to be discussed with the sponsor's medical monitor to be agreed for inclusion.
  • Estimated life expectancy of ≥3 months
  • Washout periods: 4 weeks for chemotherapy, 4 weeks or 5 half-lives (whichever shorter) for biologic agents including immuno-oncology therapy and 4 weeks from major surgeries, definitive radiotherapy and 2 weeks after palliative radiotherapy
  • At least one measurable lesion per iRECIST in a non-irradiated port. If in a previously irradiated port, must have demonstrated progression since best response to radiation therapy.
  • Have fully recovered from previous treatment to grade ≤1 toxicity (excluding alopecia) or have stable grade 2 neuropathy
  • Adequate organ system function
  • Negative serum pregnancy test, if woman of child-bearing potential (WOCBP; non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
  • Accessible tumor tissue available for fresh biopsy

Exclusion Criteria:

  • Key exclusion criteria (Part A and B)

    • Patient with untreated CNS metastases and/or leptomeningeal carcinomatosis (see list of all exclusion criteria for details)
    • Known additional malignancy that is progressing and/or requires active treatment.
    • Prior exposure to drugs that are agonists of IL-2- or IL-15-like but not limited to rhIL-15 (NCI), ALT-803 (ALTOR), NKTR-214 (Nektar)
    • History of and current interstitial lung disease or fibrosis and pneumonitis; patients with clinically significant or oxygen requiring COPD or any chronic inflammatory disease (sarcoidosis etc.)
    • Has received a live vaccine within 30 days of planned start of study therapy (see list of all exclusion criteria for details)
    • Absolute WBC count ≤ 2.0 ×109/L;
    • ALC ≤0.5×109/L
    • Absolute neutrophil count ≤1.0 ×109/L
    • Platelet count ≤100×109/L
    • Pregnant or breastfeeding women
    • Any active autoimmune disease or a documented history of autoimmune disease, poorly controlled asthma, or history of syndrome that required systemic steroids (except the allowed doses) or immunosuppressive medications, except for patients with vitiligo or resolved childhood asthma/atopy (see list of all exclusion criteria for details)
    • Specific co-morbidities (see list of all exclusion criteria for details)
    • Is hypersensitive to any of the ingredients of pembrolizumab drug product (KeytrudaTM)
    • History of solid organ transplantation or hematopoietic stem cell transplantation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Richard Kapsa (+420) 2241 74448 Kapsa@sotio.com
Listed Location Countries  ICMJE France,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04234113
Other Study ID Numbers  ICMJE SC103
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sotio a.s.
Study Sponsor  ICMJE Sotio a.s.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sotio a.s.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP