Thyroid CancerPhase 1NCT04234113
Study of Nanrilkefusp Alfa Alone and With Pembrolizumab in Adult Patients With Advanced/Metastatic Solid Tumors
A Phase 1 study testing Nanrilkefusp alfa and Pembrolizumab in people with Thyroid Cancer and Renal Cell Carcinoma, run by SOTIO Biotech AG at 12 sites in 4 countries.
Trial summary
A multicenter open-label phase 1/1b study to evaluate the safety and preliminary efficacy of nanrilkefusp alfa as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Cancer, Renal Cell Carcinoma, Non Small Cell Lung Cancer
- What is being tested?
- Nanrilkefusp alfa and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 13 Jun 2019to 27 Nov 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 performance score 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
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- Adequate organ system function
- Negative serum pregnancy test, if woman of child-bearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
- Accessible tumor tissue available for fresh biopsy
Who cannot join
- Untreated central nervous system metastases and/or leptomeningeal carcinomatosis
- 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 chronic obstructive pulmonary disease or any chronic inflammatory disease (sarcoidosis etc.)
- Has received a live vaccine within 30 days of planned start of study therapy
- Absolute white blood cell count ≤2.0 ×10e9/L
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- Absolute neutrophil count ≤1.0 ×10e9/L
- Platelet count ≤100×10e9/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
- Specific co-morbidities
- Parts B and B1:
- Is hypersensitive to any of the ingredients of pembrolizumab drug product (KEYTRUDA®)
- History of solid organ transplantation or hematopoietic stem cell transplantation
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
France6 sites
Centre Léon Bérard
Lyon, France, 69379
Hôpitaux Universitaires de Marseille Timone
Marseille, 13005
Institut Gustave Roussy
Paris, France, 94805
Hopital Saint Louis
Paris, 75010
Institut de Cancerologie de L'Ouest
Saint-Herblain, 44805
Institut Claudius Regaud
Toulouse, France, 31059
United States3 sites
MD Anderson Cancer Center
Houston, Texas, 77030
Yale Cancer Center
New Haven, Connecticut, 06520
University of Pittsburgh
Pittsburgh, Pennsylvania, 15216
Spain2 sites
Vall d'Hebron Institute of Oncology
Barcelona, Spain, 08035
University Hospital Sanchinarro
Madrid, 28050
Czechia1 site
Masarykův Onkologický Ústav Brno Klinika komplexní onkologické péče
Brno, Czechia, 65653
About this study
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
A multicenter open-label phase 1/1b study to evaluate the safety and preliminary efficacy of nanrilkefusp alfa as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors
Read the detailed description
This study will assess the safety and tolerability of nanrilkefusp alfa 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 tract cancer, hepatocellular carcinoma, ovarian cancer, gastric cancer, head and neck squamous-cell carcinoma, and anal cancer).
- Conditions
- Thyroid Cancer, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Small-cell Lung Cancer, Bladder Cancer, Melanoma
- Being tested
- Nanrilkefusp alfa, Pembrolizumab
- Keywords
- 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
- Medical subject headings
- Thyroid Neoplasms, Carcinoma, Renal Cell, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Urinary Bladder Neoplasms, Melanoma, Carcinoma, Merkel Cell, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nanrilkefusp alfaDrug
Also called SOT101, SO-C101, RLI-15
A fusion protein which consists of the N-terminal sushi domain of human IL-15 receptor α covalently coupled via a linker of 20 amino acids to human IL-15
PembrolizumabDrug
Also called KEYTRUDA®
A humanized IgG4 monoclonal antibody with high specificity of binding to the PD-1 receptor
| Study group | Role | What they receive |
|---|---|---|
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 0.25 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 0.75 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 1.5 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 3 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 6 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 9 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 12 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 15 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
| Part A1 (nanrilkefusp alfa divided dosing, monotherapy), nanrilkefusp alfa 9 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle twice a day as 2 divided doses (50%:50%) with the second dose on each treatment day administered 8 hours (±15 min) after the first dose. Receives: Drug: Nanrilkefusp alfa |
| Part A1 (nanrilkefusp alfa divided dosing, monotherapy), nanrilkefusp alfa 12 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle twice a day as 2 divided doses (50%:50%) with the second dose on each treatment day administered 8 hours (±15 min) after the first dose. Receives: Drug: Nanrilkefusp alfa |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 1.5 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose.
Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. Receives: Drug: Nanrilkefusp alfa; Drug: Pembrolizumab |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 3 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose.
Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. Receives: Drug: Nanrilkefusp alfa; Drug: Pembrolizumab |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 6 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose.
Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. Receives: Drug: Nanrilkefusp alfa; Drug: Pembrolizumab |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose.
Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. Receives: Drug: Nanrilkefusp alfa; Drug: Pembrolizumab |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 12 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose.
Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. Receives: Drug: Nanrilkefusp alfa; Drug: Pembrolizumab |
| Part B1 (nanrilkefusp alfa divided dosing, combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle twice a day as 2 divided doses (50%:50%) with the second dose on each treatment day administered 8 hours (±15 min) after the first dose.
Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. Receives: Drug: Nanrilkefusp alfa; Drug: Pembrolizumab |
| Part D (nanrilkefusp alfa monotherapy, expansion at the RP2D), nanrilkefusp alfa 12 μg/kg | Experimental | Nanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Receives: Drug: Nanrilkefusp alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities (DLTs)
- Grade (gr) 5 not related to disease progression or other causes
- Gr ≥3 non-hematologic toxicity; exceptions: gr 3 nausea, vomiting or diarrhea controlled in 72 hours; gr 3 fatigue <5 days; gr ≥3 correctable electrolyte abnormalities <72 hours and no clinical complications; gr ≥3 amylase or lipase without clinical pancreatitis
- Hy's law cases
- Gr 3 AST or ALT or gr 3 bilirubinemia >5 days
- Hematologic DLTs: gr 4 neutropenia or thrombocytopenia >7 days, febrile neutropenia, gr ≥3 thrombocytopenia with bleeding
- Gr 4 immune-related AEs
- Gr 3 or 4 non-infectious pneumonitis
- Gr 3 immune-related AEs, excluding colitis, hepatitis, and pneumonitis, not downgrading to gr ≤2 in 3 days despite maximal supportive care including systemic corticosteroids or to gr 1 or baseline in 14 days
- Gr 2 pneumonitis not downgrading to gr 1 in 3 days
- Gr 3 colitis
- Part B and Part B1: Recurrent grade 2 pneumonitis
Measured: Through Cycle 1 (21 days)
Number of Participants With Adverse Events (AEs)
Nanrilkefusp alfa related only
Measured: Day 1 up to approximately 2 years and 2.5 months
Number of Participants With Serious AEs (SAEs)
Nanrilkefusp alfa related only
Measured: Day 1 up to approximately 2 years and 2.5 months
Number of Participants With AEs Leading to Premature Discontinuation of Nanrilkefusp Alfa
Nanrilkefusp alfa related only
Measured: Day 1 up to approximately 2 years and 2.5 months
Number of Participants Who Died
Nanrilkefusp alfa-related deaths only
Measured: Day 1 up to approximately 2 years and 2.5 months
Number of Participants With Nanrilkefusp Alfa-related Clinical Laboratory Test Abnormalities (Coagulation; Hematology; Clinical Chemistry; Urinalysis; Thyroid and Cardiac Function)
The following laboratory parameters were assessed:
- Coagulation: Prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer, fibrinogen
- Hematology: Hemoglobin, hematocrit, red blood cell count, reticulocytes, white blood cell count (with full differentiation), absolute lymphocyte count, platelet count
- Clinical chemistry: Na, K, Cl, phosphate, Mg, Ca, albumin, total protein, ALT, AST, bilirubin (direct, total), alkaline phosphatase, lactate dehydrogenase, creatinine clearance, creatinine, glucose (preferably fasting), urea or blood urea nitrogen, cholesterol, triglyceride, CRP, uric acid, amylase, lipase
- Urinalysis: pH, glucose, protein, bilirubin, urobilinogen. Microscopic examination: red blood cell count, white blood cell count, epithelial cells, bacteria
- Thyroid function: TSH, free triiodothyronine (T3), free thyroxine (T4)
- Cardiac function: Cardiac troponin T
Measured: Day 1 up to approximately 2 years and 2.5 months
Secondary outcomes (12)
Nanrilkefusp Alfa Concentration Profile, Cycle 1 Day 1
This outcome measure presents the overall nanrilkefusp apfa Cmax profile over Cycle 1 Day 1.
Measured: Cycle 1 Day 1
Overall Activation Levels of Ki-67+ CD8+ T Cells on Day 6 of Cycle 1
The eCRF Hematology data (specifically white blood cell count (WBC)) for each timepoint will be used to derive the Cell counts in 10^9/L. Once merged with the pharmacodynamic data by subject and timepoint, the following will be used as derivation:
- Ki-67+ Cells of CD8+ Cells (10^9/L) = Ki-67+ Cells of CD8+ Cells (%CD45+) x 0.01 x WBC" Absolute count of Ki-67+ Cells was calculated as percentage of those cells out of CD45+ multiplied by WBC and 0.01.
Measured: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ CD8+ CD45RO+ CD45RA- T Cells on Day 6 of Cycle 1
The eCRF Hematology data (specifically white blood cell count (WBC)) for each timepoint will be used to derive the Cell counts in 10^9/L. Once merged with the pharmacodynamic data by subject and timepoint, the following will be used as derivation:
- Ki-67+ Cells of CD8+ Cells (10^9/L) = Ki-67+ Cells of CD8+ Cells (%CD45+) x 0.01 x WBC
- CD45RO+ CD45RA- (Memory) Cells of CD8+ Cells (10^9/L) = CD45RO+ CD45RA- (Memory) Cells of CD8+ Cells (%CD45+) x 0.01 x WBC Absolute count of Ki-67+ Cells was calculated as percentage of those cells out of CD45+ multiplied by WBC and 0.01.
Absolute count of CD45RO+ CD45RA- (Memory) Cells was calculated as percentage of those cells out of CD45+ multiplied by WBC and 0.01.
Measured: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ CD4+ T Cells on Day 6 of Cycle 1
The eCRF Hematology data (specifically white blood cell count (WBC)) for each timepoint will be used to derive the Cell counts in 10^9/L. Once merged with the pharmacodynamic data by subject and timepoint, the following will be used as derivation:
- Ki-67+ Cells of CD4+ Cells (10^9/L) = Ki-67+ Cells of CD4+ Cells (%CD45+) x 0.01 x WBC Absolute count of Ki-67+ Cells was calculated as percentage of those cells out of CD45+ multiplied by WBC and 0.01.
Measured: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ NK Cells on Day 6 of Cycle 1
The eCRF Hematology data (specifically white blood cell count (WBC)) for each timepoint will be used to derive the Cell counts in 10^9/L. Once merged with the pharmacodynamic data by subject and timepoint, the following will be used as derivation:
- Ki-67+ Cells of CD3-CD56+ (NK) Cells (10^9/L) = Ki-67+ Cells of CD3-CD56+ (NK) Cells (%CD45+) x 0.01 x WBC Absolute count of Ki-67+ Cells was calculated as percentage of those cells out of CD45+ multiplied by WBC and 0.01.
Measured: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ NKT Cells on Day 6 of Cycle 1
The eCRF Hematology data (specifically white blood cell count (WBC)) for each timepoint will be used to derive the Cell counts in 10^9/L. Once merged with the pharmacodynamic data by subject and timepoint, the following will be used as derivation:
- CD3+CD56+ (NKT) Cells of CD45+ Live Cells (10^9/L) = CD3+CD56+ (NKT) Cells of CD45+ Live Cells (%) x 0.01 x WBC Absolute count of Ki-67+ Cells was calculated as percentage of those cells out of Live Cells multiplied by WBC and 0.01.
Measured: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ Treg Cells on Day 6 of Cycle 1
The eCRF Hematology data (specifically white blood cell count (WBC)) for each timepoint will be used to derive the Cell counts in 10^9/L. Once merged with the pharmacodynamic data by subject and timepoint, the following will be used as derivation:
- Ki-67+ Cells of Treg Cells (10^9/L) = Ki-67+ Treg Cells (%CD45+) x 0.01 x WBC" Absolute count of Ki-67+ Cells was calculated as percentage of those cells out of CD45+ multiplied by WBC and 0.01.
Measured: Cycle 1 Day 6
Objective Response Rate
Based on investigator review of radiographic images according to Response Evaluation Criteria In Solid Tumors for immune-based therapeutics (iRECIST). Objective response rate according to iRECIST was defined as the percentage of participants with complete response according to iRECIST or partial response according to iRECIST for target lesions and assessed by CT/MRI.
Measured: Day 1 up to approximately 5 years 5 months
Duration of Response
Duration of response according to iRECIST was defined as time to disease progression for participants with partial response or complete response according to iRECIST for target lesions and assessed by CT/MRI.
Measured: Day 1 up to approximately 5 years 5 months
Clinical Benefit Rate
Based on investigator review of radiographic images according to iRECIST. Clinical benefit rate according to iRECIST was defined as the percentage of patients with partial responses, complete responses, and stable disease according to iRECIST for target lesions and assessed by CT/MRI.
Measured: Day 1 up to approximately 5 years 5 months
Progression-free Survival
Progression-free survival according to iRECIST was defined as the time from the first day of study treatment to the first date of radiological disease progression according to iRECIST or death.
Measured: Day 1 up to approximately 5 years 5 months
Number of Participants With Anti-drug Antibodies at the End of Treatment
Measured: Day 1 until 30 (±2) days after the last dose of nanrilkefusp alfa, up to approximately 5 years 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2020
- Study start13 Jun 2019
- Primary completion31 Aug 2024
- Study completion27 Nov 2024
Why it stopped: Due to lack of efficacy shown at the time of the interim analysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Thyroid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- SOTIO Biotech AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SOTIO Biotech a.s.
- Responsible party
- Sponsor
- Investigators
- Stephane Champiat, Dr., Principal investigator, Institute Gustave Roussy, Villejuif, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04234113
- Sponsor's protocol ID
- SC103
- Other IDs
- AURELIO-03, 2018-004334-15, 2018
- Status last verified
- Mar 2026
- First submitted
- 14 Nov 2019
- Last updated
- 27 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04234113
- Acronym / sponsor ID
- SC103
- Conditions
- Thyroid Cancer, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Small-cell Lung Cancer, Bladder Cancer, Melanoma
- Keywords
- Thyroid Cancer, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Small-cell Lung Cancer, Bladder Cancer, Melanoma, Merkel Cell Carcinoma, Skin Squamous Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to lack of efficacy shown at the time of the interim analysis.
- Enrolment
- 115 participants (actual)
- Lead sponsor
- SOTIO Biotech AGIndustry (pharma, biotech, devices)
- Collaborators
- SOTIO Biotech a.s.
- Study start
- 13 Jun 2019 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 27 Nov 2024 (actual)
- First posted
- 21 Jan 2020 (actual)
- Results
- Posted 27 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multicenter open-label phase 1/1b study to evaluate the safety and preliminary efficacy of nanrilkefusp alfa 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 nanrilkefusp alfa 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 tract cancer, hepatocellular carcinoma, ovarian cancer, gastric cancer, head and neck squamous-cell carcinoma, and anal cancer).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 17
| Arm | Type | Receives |
|---|---|---|
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 0.25 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 0.75 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 1.5 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 3 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 6 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 9 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 12 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 15 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
| Part A1 (nanrilkefusp alfa divided dosing, monotherapy), nanrilkefusp alfa 9 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle twice a day as 2 divided doses (50%:50%) with the second dose on each treatment day administered 8 hours (±15 min) after the first dose. |
| Part A1 (nanrilkefusp alfa divided dosing, monotherapy), nanrilkefusp alfa 12 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle twice a day as 2 divided doses (50%:50%) with the second dose on each treatment day administered 8 hours (±15 min) after the first dose. |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 1.5 μg/kg | Experimental | Drug: Nanrilkefusp alfa, Drug: PembrolizumabNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 3 μg/kg | Experimental | Drug: Nanrilkefusp alfa, Drug: PembrolizumabNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 6 μg/kg | Experimental | Drug: Nanrilkefusp alfa, Drug: PembrolizumabNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg | Experimental | Drug: Nanrilkefusp alfa, Drug: PembrolizumabNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. |
| Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 12 μg/kg | Experimental | Drug: Nanrilkefusp alfa, Drug: PembrolizumabNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. |
| Part B1 (nanrilkefusp alfa divided dosing, combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg | Experimental | Drug: Nanrilkefusp alfa, Drug: PembrolizumabNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle twice a day as 2 divided doses (50%:50%) with the second dose on each treatment day administered 8 hours (±15 min) after the first dose. Pembrolizumab 200 mg was administered intravenously on day 1 of the 21-day treatment cycle. |
| Part D (nanrilkefusp alfa monotherapy, expansion at the RP2D), nanrilkefusp alfa 12 μg/kg | Experimental | Drug: Nanrilkefusp alfaNanrilkefusp alfa was administered on day 1 (±1 day), day 2, day 8, and day 9 of the 21-day treatment cycle as a once-daily dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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 performance score 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.
Key exclusion criteria (14 listed)
- Untreated central nervous system metastases and/or leptomeningeal carcinomatosis
- 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 chronic obstructive pulmonary disease or any chronic inflammatory disease (sarcoidosis etc.)
- Has received a live vaccine within 30 days of planned start of study therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nanrilkefusp alfaAlso: SOT101, SO-C101, RLI-15A fusion protein which consists of the N-terminal sushi domain of human IL-15 receptor α covalently coupled via a linker of 20 amino acids to human IL-15 | Drug | Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 0.25 μg/kg, Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 0.75 μg/kg, Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 1.5 μg/kg, Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 12 μg/kg, Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 15 μg/kg, Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 3 μg/kg, Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 6 μg/kg, Part A (nanrilkefusp alfa monotherapy), nanrilkefusp alfa 9 μg/kg, Part A1 (nanrilkefusp alfa divided dosing, monotherapy), nanrilkefusp alfa 12 μg/kg, Part A1 (nanrilkefusp alfa divided dosing, monotherapy), nanrilkefusp alfa 9 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 1.5 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 12 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 3 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 6 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg, Part B1 (nanrilkefusp alfa divided dosing, combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg, Part D (nanrilkefusp alfa monotherapy, expansion at the RP2D), nanrilkefusp alfa 12 μg/kg |
| PembrolizumabAlso: KEYTRUDA®A humanized IgG4 monoclonal antibody with high specificity of binding to the PD-1 receptor | Drug | Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 1.5 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 12 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 3 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 6 μg/kg, Part B (nanrilkefusp alfa combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg, Part B1 (nanrilkefusp alfa divided dosing, combined with pembrolizumab), nanrilkefusp alfa 9 μg/kg |
Primary outcome
Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Through Cycle 1 (21 days)
* Grade (gr) 5 not related to disease progression or other causes * Gr ≥3 non-hematologic toxicity; exceptions: gr 3 nausea, vomiting or diarrhea controlled in 72 hours; gr 3 fatigue <5 days; gr ≥3 correctable electrolyte abnormalities <72 hours and no clinical complications; gr ≥3 amylase or lipase without clinical pancreatitis * Hy's law cases * Gr 3 AST or ALT or gr 3 bilirubinemia >5 days * Hematologic DLTs: gr 4 neutropenia or thrombocytopenia >7 days, febrile neutropenia, gr ≥3 thrombocytopenia with bleeding * Gr 4 immune-related AEs * Gr 3 or 4 non-infectious pneumonitis * Gr 3 immune-related AEs, excluding colitis, hepatitis, and pneumonitis, not downgrading to gr ≤2 in 3 days despite maximal supportive care including systemic corticosteroids or to gr 1 or baseline in 14 days * Gr 2 pneumonitis not downgrading to gr 1 in 3 days * Gr 3 colitis * Part B and Part B1: Recurrent grade 2 pneumonitis
Number of Participants With Adverse Events (AEs)
Time frame: Day 1 up to approximately 2 years and 2.5 months
Nanrilkefusp alfa related only
Number of Participants With Serious AEs (SAEs)
Time frame: Day 1 up to approximately 2 years and 2.5 months
Nanrilkefusp alfa related only
Number of Participants With AEs Leading to Premature Discontinuation of Nanrilkefusp Alfa
Time frame: Day 1 up to approximately 2 years and 2.5 months
Nanrilkefusp alfa related only
Number of Participants Who Died
Time frame: Day 1 up to approximately 2 years and 2.5 months
Nanrilkefusp alfa-related deaths only
Number of Participants With Nanrilkefusp Alfa-related Clinical Laboratory Test Abnormalities (Coagulation; Hematology; Clinical Chemistry; Urinalysis; Thyroid and Cardiac Function)
Time frame: Day 1 up to approximately 2 years and 2.5 months
The following laboratory parameters were assessed: * Coagulation: Prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer, fibrinogen * Hematology: Hemoglobin, hematocrit, red blood cell count, reticulocytes, white blood cell count (with full differentiation), absolute lymphocyte count, platelet count * Clinical chemistry: Na, K, Cl, phosphate, Mg, Ca, albumin, total protein, ALT, AST, bilirubin (direct, total), alkaline phosphatase, lactate dehydrogenase, creatinine clearance, creatinine, glucose (preferably fasting), urea or blood urea nitrogen, cholesterol, triglyceride, CRP, uric acid, amylase, lipase * Urinalysis: pH, glucose, protein, bilirubin, urobilinogen. Microscopic examination: red blood cell count, white blood cell count, epithelial cells, bacteria * Thyroid function: TSH, free triiodothyronine (T3), free thyroxine (T4) * Cardiac function: Cardiac troponin T
12 secondary outcomes
Nanrilkefusp Alfa Concentration Profile, Cycle 1 Day 1
Time frame: Cycle 1 Day 1
Overall Activation Levels of Ki-67+ CD8+ T Cells on Day 6 of Cycle 1
Time frame: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ CD8+ CD45RO+ CD45RA- T Cells on Day 6 of Cycle 1
Time frame: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ CD4+ T Cells on Day 6 of Cycle 1
Time frame: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ NK Cells on Day 6 of Cycle 1
Time frame: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ NKT Cells on Day 6 of Cycle 1
Time frame: Cycle 1 Day 6
Overall Activation Levels of Ki-67+ Treg Cells on Day 6 of Cycle 1
Time frame: Cycle 1 Day 6
Objective Response Rate
Time frame: Day 1 up to approximately 5 years 5 months
Duration of Response
Time frame: Day 1 up to approximately 5 years 5 months
Clinical Benefit Rate
Time frame: Day 1 up to approximately 5 years 5 months
Progression-free Survival
Time frame: Day 1 up to approximately 5 years 5 months
Number of Participants With Anti-drug Antibodies at the End of Treatment
Time frame: Day 1 until 30 (±2) days after the last dose of nanrilkefusp alfa, up to approximately 5 years 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephane Champiat, Dr. principal investigator
Institute Gustave Roussy, Villejuif, France
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nanrilkefusp alfa and Pembrolizumab in people with Thyroid Cancer and Renal Cell Carcinoma, run by SOTIO Biotech AG at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France, United States, Spain, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Through Cycle 1 (21 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.