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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Thymic Cancer, Mesothelioma, 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, Cervical Cancer, Biliary Tract Cancer, Hepatocellular Carcinoma, Ovarian Cancer, Gastric Cancer, Head and Neck Squamous Cell Carcinoma, Anal Cancer

Intervention / Treatment
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* Drug: SO-C101
* Drug: pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Part A (SO-C101 Monotherapy)<br>Drug: SO-C101 | Drug: SO-C101<br>* SO-C101<br>* Other names: SOT101;|
| Experimental: Experimental: Part B (SO-C101 combined with pembrolizumab)<br>Drug: SO-C101 Drug: pembrolizumab | Drug: SO-C101<br>* SO-C101<br>* Other names: SOT101;Drug: pembrolizumab<br>* pembrolizumab<br>|
| Experimental: Experimental: Part A1 (SO-C101 divided dosing, Monotherapy)<br>Drug: SO-C101, twice a day as 2 divided doses (50%:50%) | Drug: SO-C101<br>* SO-C101<br>* Other names: SOT101;|
| Experimental: Experimental: Part B1 (SO-C101 divided dosing, combined with pembrolizumab)<br>Drug: SO-C101, twice a day as 2 divided doses (50%:50%) Drug: pembrolizumab | Drug: SO-C101<br>* SO-C101<br>* Other names: SOT101;Drug: pembrolizumab<br>* pembrolizumab<br>|
| Experimental: Experimental: Part D (SO-C101 Monotherapy, dose expansion at the RP2D identified in Part A)<br>Drug: SO-C101 Indications: Relapsed/refractory advanced/metastatic renal cell carcinoma, relapsed/refractory advanced/metastatic skin squamous-cell carcinoma, and relapsed/refractory advanced/metastatic melanoma. | Drug: SO-C101<br>* SO-C101<br>* Other names: SOT101;|
| Experimental: Part D1 (SO-C101 divided dosing, Monotherapy, dose expansion at RP2D identified in Part A1)<br>Drug: SO-C101, twice a day as 2 divided doses (50%:50%) Indications: Relapsed/refractory advanced/metastatic renal cell carcinoma, relapsed/refractory advanced/metastatic skin squamous-cell carcinoma, and relapsed/refractory advanced/metastatic melanoma. | Drug: SO-C101<br>* SO-C101<br>* Other names: SOT101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A;Number of Participants With Dose-Limiting Toxicities (DLT): | 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 | Through Cycle 1 (a cycle is 21 days] | 
| Part A;Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Cycle 1, Day 1 (each cycle is 21 days) through study completion an average of 1 year | 
| Part A;Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs | 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 | assessed in average of 7 months | 
| 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 | 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 | assessed in average of 7 months | 
| 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 | 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. | Cycle 1 Day 1 (each cycle is 21 days) through study completion, an average of 1 year | 
| Part A;Number of Participants With Laboratory Test Abnormalities: Urinalysis | 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 | Cycle 1 Day 1, (each cycle is 21 days) through study completion, an average of 1 year | 
| Part A;Number of Participants With Clinically Significant Change From Screening in Vital Signs | 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 | Screening, through study completion, an average of 1 year | 
| Part A; Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score | 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. | Screening, through study completion, an average of 1 year | 
| Part B: Number of Participants With Dose-Limiting Toxicities (DLT): Dose Finding Phase | 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 | Cycle 1 Day 1 to Cycle 2 Day 1 21 days | 
| Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events | 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 | Cycle 1 Day 1, up to 90 days after last dose of study drug (assessed in average of 7 months | 
| Part B: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events | 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 | Cycle 1 Day 1, up to 90 days after last dose of study drug (assessed in average of 7 months | 
| 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 | 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. | Cycle 1 Day 1, (each cycle is 21 days) through study completion, an average of 1 year | 
| 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 | 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. | Cycle 1 Day 1, (each cycle is 21 days) through study completion, an average of 1 year | 
| Part B: Number of Participants With Laboratory Test Abnormalities: Urinalysis | 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 | Screening, through study completion, an average of 1 year | 
| Part B: Number of Participants With Clinically Significant Change From Screening in Vital Signs | 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. | Screening, through study completion, an average of 1 year | 
| Part B: Number of Participants With Eastern Cooperative Oncology Group [ECOG] | 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. | Screening, through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A PK parameters | Assess plasma concentration of SO-C101 at various timepoints | assessed in average of 2 months | 
| Part A Objective response rate (ORR) | based on investigator review of radiographic images according to iRECIST | assessed in average of 5 months | 
| Part A Best overall response (BOR) | BOR by iRECIST | assessed in average of 5 months | 
| Part A Duration of Response (DOR) | DOR by iRECIST | assessed in average of 5 months | 
| Part A Clinical benefit rate (CBR) | CBR by iRECIST | assessed in average of 5 months | 
| Part A Progression-Free Survival (PFS) | PFS by iRECIST | assessed in average of 5 months | 
| Part A Immunogenicity analysis to assess antibodies to SO-C101 in human serum | to assess antibodies to SO-C101 in human serum | assessed in average of 4 months | 
| Part B PK parameters of SO-C101 administered in combination with pemrolizumab | Assess plasma concentration of SO-C101 (administered in combination with pembrolizumab) at various timepoints | assessed in average of 2 months | 
| Part B Objective response rate (ORR) | SO-C101combined with pemrolizumab based on investigator review of radiographic images according to iRECIST | assessed in average of 5 months | 
| Part B Best overall response (BOR) of SO-C101 | combined with pemrolizumab by iRECIST | assessed in average of 5 months | 
| Part B Duration of Response (DOR) | of SO-C101 combined with pembrolizumab by iRECIST | assessed in average of 5 months | 
| Part B Clinical benefit rate (CBR) | of SO-C101 combined with by iRECIST | assessed in average of 5 months | 
| Part B Progression-Free Survival (PFS) | of SO-C101combined with pemrolizumab by iRECIST | assessed in average of 5 months | 
| Immunogenicity analysis to assess antibodies to SO-C101 | SO-C101 in human serum | assessed in average of 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Head and Neck Squamous Cell Carcinoma, 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, Anal Cancer