Study of Nanrilkefusp Alfa Alone and With Pembrolizumab in Adult Patients With Advanced/Metastatic Solid Tumors

NCT04234113 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: SC103AURELIO-032018-004334-15
• Study Type: interventional
• Target: 115
• Locations: 4 countries
• Sites: 12

Brief 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

Conditions

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

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

Outcome Measures

Primary Outcomes (6)

• 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

  Through Cycle 1 (21 days)

• Number of Participants With Adverse Events (AEs)

  Nanrilkefusp alfa related only

  Day 1 up to approximately 2 years and 2.5 months

• Number of Participants With Serious AEs (SAEs)

  Nanrilkefusp alfa related only

  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

  Day 1 up to approximately 2 years and 2.5 months

• Number of Participants Who Died

  Nanrilkefusp alfa-related deaths only

  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

  Day 1 up to approximately 2 years and 2.5 months

Secondary Outcomes (12)

• Nanrilkefusp Alfa Concentration Profile, Cycle 1 Day 1

  Cycle 1 Day 1

• Overall Activation Levels of Ki-67+ CD8+ T Cells on Day 6 of Cycle 1

  Cycle 1 Day 6

• Overall Activation Levels of Ki-67+ CD8+ CD45RO+ CD45RA- T Cells on Day 6 of Cycle 1

  Cycle 1 Day 6

• Overall Activation Levels of Ki-67+ CD4+ T Cells on Day 6 of Cycle 1

  Cycle 1 Day 6

• Overall Activation Levels of Ki-67+ NK Cells on Day 6 of Cycle 1

  Cycle 1 Day 6

Study Arms (17)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug: Nanrilkefusp alfa

Interventions

Nanrilkefusp alfa DRUG

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

Also known as: SOT101, SO-C101, RLI-15

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

Pembrolizumab DRUG

A humanized IgG4 monoclonal antibody with high specificity of binding to the PD-1 receptor

Also known as: KEYTRUDA®

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
• Accessible tumor tissue available for fresh biopsy

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• SOTIO Biotech AG: lead
• SOTIO Biotech a.s.: collaborator

Study Sites (12)

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15216, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Masarykův Onkologický Ústav Brno Klinika komplexní onkologické péče

Brno, Czechia, 65653, Czechia

Location

Centre Léon Bérard

Lyon, France, 69379, France

Location

Institut Gustave Roussy

Paris, France, 94805, France

Location

Institut Claudius Regaud

Toulouse, France, 31059, France

Location

Hôpitaux Universitaires de Marseille Timone

Marseille, 13005, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Institut de Cancerologie de L'Ouest

Saint-Herblain, 44805, France

Location

Vall d'Hebron Institute of Oncology

Barcelona, Spain, 08035, Spain

Location

University Hospital Sanchinarro

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

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; Mesothelioma; Thymus Neoplasms; Uterine Cervical Neoplasms; Biliary Tract Neoplasms; Carcinoma, Hepatocellular; Ovarian Neoplasms; Stomach Neoplasms; Squamous Cell Carcinoma of Head and Neck; Anus Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Urinary Bladder Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Breast Neoplasms; Breast Diseases; Adenoma; Neoplasms, Mesothelial; Lymphatic Diseases; Hemic and Lymphatic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Liver Neoplasms; Liver Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Carcinoma, Squamous Cell; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Intestinal Diseases; Anus Diseases; Rectal Diseases

Results Point of Contact

• Title: Richard Kapsa
• Organization: SOTIO Biotech a.s.

kapsa@sotio.com

(+420) 2241 74448

Study Officials

• Stephane Champiat, Dr.

  Institute Gustave Roussy, Villejuif, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: January 21, 2020
• Study Start: June 13, 2019
• Primary Completion: August 31, 2024
• Study Completion: November 27, 2024
• Last Updated: March 27, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6); ES (2); CZ (1); US (3)