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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04234113
• Other study ID #: SC103
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 13, 2019
• Est. completion date: November 2024

Study information

• Verified date: September 2023
• Source: Sotio Biotech Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: November 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms
• Biliary Tract Cancer
• Biliary Tract Neoplasms
• Bladder Cancer
• Carcinoma
• Carcinoma, Hepatocellular
• Carcinoma, Merkel Cell
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Carcinoma, Squamous Cell
• Cervical Cancer
• Gastric Cancer
• Head and Neck Squamous Cell Carcinoma
• Hepatocellular Carcinoma
• Lung Neoplasms
• Melanoma
• Merkel Cell Carcinoma
• Mesothelioma
• Mesothelioma, Malignant
• Microsatellite Instability
• Microsatellite Instability High
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Renal Cell Carcinoma
• Skin Squamous Cell Carcinoma
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• Stomach Neoplasms
• Thymic Cancer
• Thymus Neoplasms
• Thyroid
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urinary Bladder Neoplasms
• Uterine Cervical Neoplasms

Intervention

Drug:
• SO-C101
SO-C101
• pembrolizumab
pembrolizumab

Locations

Country	Name	City	State
Czechia	Masarykuv Onkologický Ústav Brno Klinika komplexní onkologické péce	Brno
France	Centre Léon Bérard	Lyon
France	Hôpitaux Universitaires de Marseille Timone	Marseille
France	Hopital Saint Louis	Paris
France	Institut Gustave Roussy	Paris
France	Institut de Cancerologie de L'Ouest	Saint Herblain
France	Institut Claudius Regaud	Toulouse
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	University Hospital Sanchinarro	Madrid
United States	MD Anderson Cancer Center	Houston	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
SOTIO Biotech AG	SOTIO Biotech a.s.

Countries where clinical trial is conducted

United States,  Czechia,  France,  Spain, 

Outcome

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