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Study of SO-C101 and SO-C101in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04234113
Recruitment Status : Recruiting
First Posted : January 21, 2020
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Sotio a.s.

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

Condition or disease Intervention/treatment Phase
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 Drug: SO-C101 Drug: pembrolizumab Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 13, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Experimental: Experimental: Part A (SO-C101 Monotherapy)
Drug: SO-C101
Drug: SO-C101
SO-C101

Experimental: Experimental: Part B (SO-C101 combined with pembrolizumab)
Drug: SO-C101 Drug: pembrolizumab
Drug: SO-C101
SO-C101

Drug: pembrolizumab
pembrolizumab




Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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


  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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


  15. 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.

  16. 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.


Secondary Outcome Measures :
  1. Part A PK parameters [ Time Frame: assessed in average of 2 months ]
    Assess plasma concentration of SO-C101 at various timepoints

  2. Part A Objective response rate (ORR) [ Time Frame: assessed in average of 5 months ]
    based on investigator review of radiographic images according to iRECIST

  3. Part A Best overall response (BOR) [ Time Frame: assessed in average of 5 months ]
    BOR by iRECIST

  4. Part A Duration of Response (DOR) [ Time Frame: assessed in average of 5 months ]
    DOR by iRECIST

  5. Part A Clinical benefit rate (CBR) [ Time Frame: assessed in average of 5 months ]
    CBR by iRECIST

  6. Part A Progression-Free Survival (PFS) [ Time Frame: assessed in average of 5 months ]
    PFS by iRECIST

  7. 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

  8. 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

  9. 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

  10. Part B Best overall response (BOR) of SO-C101 [ Time Frame: assessed in average of 5 months ]
    combined with pemrolizumab by iRECIST

  11. Part B Duration of Response (DOR) [ Time Frame: assessed in average of 5 months ]
    of SO-C101 combined with pembrolizumab by iRECIST

  12. Part B Clinical benefit rate (CBR) [ Time Frame: assessed in average of 5 months ]
    of SO-C101 combined with by iRECIST

  13. Part B Progression-Free Survival (PFS) [ Time Frame: assessed in average of 5 months ]
    of SO-C101combined with pemrolizumab by iRECIST

  14. Immunogenicity analysis to assess antibodies to SO-C101 [ Time Frame: assessed in average of 4 months ]
    SO-C101 in human serum



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04234113


Contacts
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Contact: Richard Kapsa (+420) 2241 74448 Kapsa@sotio.com

Locations
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United States, Connecticut
Yale Cancer Center Not yet recruiting
New Haven, Connecticut, United States, 06520
Contact: Patricia LoRusso, MD, Ph.D    203-785-5944    patricia.lorusso@yale.edu   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Filip Janku, MD, Pd.D    713-563-2632    FJanku@mdanderson.org   
France
Institut Gustave Roussy Recruiting
Paris, France, 94805
Spain
Vall d'Hebron Institute of Oncology Recruiting
Barcelona, Spain, 08035
Sponsors and Collaborators
Sotio a.s.
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Responsible Party: Sotio a.s.
ClinicalTrials.gov Identifier: NCT04234113    
Other Study ID Numbers: SC103
First Posted: January 21, 2020    Key Record Dates
Last Update Posted: January 21, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sotio a.s.:
thyroid cancer
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
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma, Squamous Cell
Ovarian Neoplasms
Carcinoma, Hepatocellular
Stomach Neoplasms
Uterine Cervical Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Small Cell Lung Carcinoma
Mesothelioma
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Biliary Tract Neoplasms
Anus Neoplasms
Thymus Neoplasms
Microsatellite Instability
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases