E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced/refractory solid tumors |
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E.1.1.1 | Medical condition in easily understood language |
advanced/refractory solid tumors. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029514 |
E.1.2 | Term | Non-small cell lung cancer NOS |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 24.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10085908 |
E.1.2 | Term | Cutaneous squamous cell carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019829 |
E.1.2 | Term | Hepatocellular carcinoma recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076506 |
E.1.2 | Term | Castration-resistant prostate cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033130 |
E.1.2 | Term | Ovarian cancer NOS |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the antitumor efficacy of SOT101 in combination with pembrolizumab |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of SOT101 in combination with pembrolizumab according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. To further evaluate the antitumor efficacy of SOT101 in combination with pembrolizumab. (Population) pharmacokinetics (PK) of SOT101 in combination with pembrolizumab.To determine the immunogenicity of SOT101 in combination with pembrolizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Be 18 years of age on the day of signing informed consent 2.Ability to understand and sign written informed consent to participate in the study 3.Provides written informed consent for the study 4.Patients with the following histologically or cytologically confirmed solid tumor indications and line of treatment: •NSCLC •Colorectal cancer •cSCC •Advanced hepatocellular carcinoma • mCRPC •Ovarian cancer 5.Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology; lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. mCRPC: Patients with both measurable and non-measurable disease will be enrolled. At least 35 patients with measurable disease will be enrolled. Patients with no measurable disease and only widespread bone disease must have a CTC count of >5 cells per 7.5 mL of blood. 6.Accessible tumor tissue available for fresh biopsy except for mCRPC with no accessible tumor tissue 7.Performance status: Eastern Cooperative Oncology Group (ECOG) performance score 0-1 8.Must have recovered from all AEs (except alopecia) due to previous therapies to grade ≤1 toxicity (excluding alopecia) or have stable grade 2 neuropathy Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of study interventions. 9.Hematology: 9.1. Absolute neutrophil count ≥1500/µL 9.2. Platelets ≥100 000/µL 9.3. Hemoglobin ≥9.0 g/dL (criteria must be met without packed red blood cell transfusion within the prior 2 weeks; patients can be on a stable dose of erythropoietin [≥ 3 months]) 10.Renal function: Creatinine clearance as measured by glomerular filtration rate ≥30 mL/min using Cockcroft-Gault equation 11.Hepatic function: Alanine transaminase (ALT)/aspartate transaminase (AST) ≤2.5× upper limit of normal (ULN) and total bilirubin ≤1.5×ULN or direct bilirubin ≤ ULN in patients without liver metastasis (benign hereditary hyperbilirubinemias). In patients with liver metastasis, ALT/AST ≤5×ULN is allowed but total bilirubin must be ≤2×ULN. 12.Prothrombin time and activated partial thromboplastin time ≤1.5×ULN 13.Patients who are hepatitis B (HBV) surface antigen positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load before study entry (ICF signature). 14.Patients with history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening. Patients must have completed anti-viral therapy at least 4 weeks before study entry (ICF signature). 15.A female patient is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies: 15.1.Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is insufficient. 15.2.A WOCBP who agrees to use a highly effective contraceptive method during the treatment period and for at least 120 days after the last dose of pembrolizumab or at least 30 days after the last dose of SOT101, whichever is later. • WOCBP can only be included after a negative serum pregnancy test at screening. • Highly effective contraception includes: o Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: Oral Intravaginal Transdermal o Progestogen-only hormonal contraception associated with inhibition of ovulation: Oral Injectable Implantable oIntrauterine device oIntrauterine hormone-releasing system oBilateral tubal occlusion oVasectomized partner provided the partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success. oSexual abstinence defined as refraining from heterosexual intercourse during the entire treatment period and for at least 120 days after the last dose of pembrolizumab or at least 30 days after the last dose of SOT101, whichever is later. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. 16. Male patients must agree to use a condom during the treatment period and for at least 120 days after the last dose of pembrolizumab or at least 30 days after the last dose of SOT101, whichever is later.
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E.4 | Principal exclusion criteria |
1.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a grade ≥3 AE 2.Prior exposure to drugs that are agonists of IL-2 or IL-15 3.Prior systemic anti-cancer therapies, including investigational agents, before study entry (ICF signature): 3.1. Less than 4 weeks for systemic chemotherapy and immuno-oncology therapies; and for tyrosine kinase inhibitors 4 weeks or 5 half-lives (whichever is shorter) 3.2. Less than 4 weeks from major surgeries and not recovered adequately from the procedure and/or any complications from the surgery 4.Has received prior radiotherapy within 2 weeks of the start of study interventions. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system disease. 5.NSCLC indication only: Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study interventions 6.Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study interventions Prior/concurrent clinical study experience 7.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks or 5 half lives (whichever shorter) before study entry (ICF signature). Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or 5 half lives (whichever shorter) after the last dose of the previous investigational agent. 8.Clinically significant cardiac abnormalities including prior history of any of the following: 8.1. Cardiomyopathy, with left ventricular ejection fraction ≤50% at screening 8.2. Congestive heart failure of New York Heart Association grade ≥2 8.3. History of clinically significant, atherosclerotic cardiovascular disease, specifically myocardial infarction, unstable angina, cerebrovascular accident within 6 months prior to the first dose of study interventions, and any history of coronary heart disease and clinically significant peripheral and/or carotid artery disease 8.4.Prolongation of QTcF >450 msec 8.5.Clinically significant cardiac arrythmia that cannot be controlled with adequate medication 9.Uncontrolled hypertension defined as systolic blood pressure >160 mmHg, diastolic blood pressure >110 mmHg. Patients with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry (ICF signature). 10. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. 11.Has had an allogeneic tissue/solid organ transplant 12.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study interventions 13.History of or serology positive for HIV 14.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Patients with basal cell carcinoma of the skin or carcinoma in situ that have undergone potentially curative therapy are not excluded. 15.Has known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of study interventions. 16.Has severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of its excipients 17.Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 18. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease 19.Has an active infection requiring systemic therapy 20.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator 21.Has a known psychiatric or substance abuse disorder that would interfere with the patient’s ability to cooperate with the requirements of the study
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E.5 End points |
E.5.1 | Primary end point(s) |
• Objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) in patients with measurable disease |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Type, frequency, and severity of treatment-emergent adverse events (TEAEs); adverse events of special interest (AESIs); safety laboratory findings; vital signs; electrocardiography (ECG) findings; • ORR according to RECIST for immune-based therapeutics (iRECIST) (iORR) in patients with measurable disease • Best overall response according to RECIST 1.1 (BOR) and iRECIST (iBOR) in patients with measurable disease • Duration of response according to RECIST 1.1 (DoR), iRECIST (iDoR), and Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified RECIST 1.1 (metastatic castration-resistant prostate cancer [mCRPC] only) • Clinical benefit rate according to RECIST 1.1 (CBR), iRECIST (iCBR), and PCWG3-modified RECIST 1.1 (mCRPC only) • Progression-free survival (PFS) according to RECIST 1.1, iRECIST (iPFS), and PCWG3-modified RECIST 1.1 (mCRPC only) • Time to response according to RECIST 1.1 (TtR) and iRECIST (iTtR) in patients with measurable disease • mCRPC only: o Circulating tumor cell (CTC) count conversion from >5 to <5 cells per 7.5 mL of blood o Confirmed prostate-specific antigen (PSA) decline of ≥50% o Time to confirmed PSA progression • Plasma concentrations of SOT101 over time; • Incidence, titer, and time course of anti-drug antibodies (ADAs) against SOT101 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Georgia |
United States |
Belgium |
Czechia |
France |
Germany |
Italy |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will end one year after the last patient’s last dose of SOT101 and/or pembrolizumab (whichever occurs later). A patient is considered to have completed the study if s/he has completed all phases of the study including the last follow-up contact |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 12 |