nanrilkefusp alfa (SOT101) / Sotio - LARVOL DELTA

Nanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers. (PubMed, Cell Rep Med) - P1 | "It had a favorable safety profile when administered subcutaneously on days 1, 2, 8, and 9 of each 21-day cycle as monotherapy (0.25-15 μg/kg) or combined (1.5-12 μg/kg) with the anti-PD-1 pembrolizumab (200 mg). The most frequent treatment-emergent adverse events were pyrexia, injection site reactions, and chills. Furthermore, early clinical efficacy was observed, including in immune checkpoint blockade-resistant/refractory patients."

Journal • Oncology • Solid Tumor • CD8 • IL15

AURELIO-03: Study of Nanrilkefusp Alfa Alone and With Pembrolizumab in Adult Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=115 | Terminated | Sponsor: SOTIO Biotech AG | N=200 ➔ 115 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Aug 2024; Due to lack of efficacy shown at the time of the interim analysis.

Enrollment change • Monotherapy • Trial primary completion date • Trial termination • Anal Carcinoma • Biliary Cancer • Bladder Cancer • Breast Cancer • Cervical Cancer • Endocrine Cancer • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thymus Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer

KEYNOTE-D13: A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=166 | Terminated | Sponsor: SOTIO Biotech AG | Active, not recruiting ➔ Terminated; Due to lack of expected efficacy shown at the time of the interim analysis

Metastases • Trial termination • Castration-Resistant Prostate Cancer • Colorectal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

SOT201, a novel cis-acting PD-1/IL-15 mutein-based immunocytokine that reinvigorates anti-tumor immunity qualitatively superior to PD-1/IL-2v-based IL-2/15Rβγ agonism (SITC 2024) - P1 | "Results SOT201 delivers attenuated RLI-15 mutein to PD1+ T cells via cis presentation, reinvigorates exhausted human T cells and induces a higher IFN-γ production than pembrolizumab in vitro. 246/1992. Some studies were performed according to animal welfare regulations by CrownBio (Bejing, China)."

Oncology • CD8 • IFNG • IL15 • IL2 • PD-1 • STK11

VICTORIA-01: a multicenter, open-label, phase 1 study to evaluate the safety and preliminary efficacy of SOT201 in patients with advanced or metastatic solid tumors (SITC 2024) - P1 | "Background SOT201 is an immunocytokine consisting of a humanized monoclonal antibody against programmed cell death protein 1 (PD-1) and a low-activity variant of a receptor-linker-interleukin-15 fusion protein (RLI-15). A total of 40 patients are expected to be recruited.A Bayesian logistic regression model will be used to select the minimum reproducibly active dose (MRAD), maximum administered dose (MAD), effective dose approximating the maximum tolerated dose (MTD), and recommended phase 2 doses (RP2Ds), as appropriate.The main inclusion criteria are histologically or cytologically confirmed advanced or metastatic solid tumors; intolerance to or ineligibility for all available therapies; no liver metastases; measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; tumor tissue accessible for biopsy; and Eastern Cooperative Oncology Group performance score 0–1.The primary endpoints are the type, frequency, and severity of..."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • CD8 • IL15

AURELIO-03: Study of Nanrilkefusp Alfa Alone and With Pembrolizumab in Adult Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=200 | Active, not recruiting | Sponsor: SOTIO Biotech AG | Trial primary completion date: Aug 2024 ➔ Dec 2024

Combination therapy • Metastases • Monotherapy • Trial primary completion date • Anal Carcinoma • Biliary Cancer • Bladder Cancer • Breast Cancer • Cervical Cancer • Endocrine Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thymus Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer

KEYNOTE-D13: A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=166 | Active, not recruiting | Sponsor: SOTIO Biotech AG | Trial completion date: Dec 2025 ➔ Nov 2024 | Trial primary completion date: Sep 2025 ➔ Aug 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

AURELIO-05: A Study of Nanrilkefusp Alfa (SOT101) in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: SOTIO Biotech AG | N=52 ➔ 16 | Trial completion date: Nov 2024 ➔ Jun 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Mar 2024; Due to lack of efficacy shown at the time of the interim analysis.

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

KEYNOTE-D13: A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=166 | Active, not recruiting | Sponsor: SOTIO Biotech AG | N=320 ➔ 166 | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Apr 2025 ➔ Sep 2025

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

KEYNOTE-D13: A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=320 | Active, not recruiting | Sponsor: SOTIO Biotech AG | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2023 ➔ Apr 2025

Combination therapy • Enrollment closed • Metastases • Trial primary completion date • Castration-Resistant Prostate Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

AURELIO-03: Study of SO-C101 and SO-C101 in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=200 | Active, not recruiting | Sponsor: SOTIO Biotech AG | Trial completion date: Dec 2023 ➔ Nov 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Anal Carcinoma • Biliary Cancer • Bladder Cancer • Breast Cancer • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thymus Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer

AURELIO-05: A Study of Nanrilkefusp Alfa (SOT101) in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer (clinicaltrials.gov) - P2 | N=52 | Active, not recruiting | Sponsor: SOTIO Biotech AG | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2025 ➔ Nov 2024 | Trial primary completion date: Nov 2025 ➔ Aug 2024

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Combination with IL-15Rβγ superagonist, Nanrilkefusp alfa, enhances CAR T and BOXR T cell anti-tumor activity (SITC 2023) - "Background Nanrilkefusp alfa (Nanril, SOT101) is an IL-15Rβγ superagonist that is comprised of the IL15 cytokine fused to the IL-15Rα and has demonstrated a favorable safety profile and encouraging efficacy signals as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) in the Phase 1/1b AURELIO-03 trial. Conclusions These data demonstrate that combination of Nanril with BOXR-T and CAR-T cells results in improved T cell function and anti-tumor activity in preclinical models. Combination of Nanril with T cell-based therapies may be a promising approach to increase efficacy in difficult-to-treat solid tumors."

Oncology • Solid Tumor • IL15

Nanrilkefusp alfa, a high-affinity IL-15Rβγ agonist, promotes an innate and adaptive anti-tumour inflammatory environment as single agent or combined with anti-PD-1 in patients with advanced cancers (SITC 2023) - P1, P2 | "Background Nanrilkefusp alfa (SOT101, RLI-15) is a high affinity superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain representing a promising clinical candidate for the treatment of cancer. Conclusions Nanrilkefusp alfa boosts both the innate and adaptive immune system and induces proinflammatory changes in the microenvironment of multiple tumor types as single-agent and in combination with pembrolizumab. An extended evaluation of nanrilkefusp alfa in combination with pembrolizumab or cetuximab is currently ongoing in phase 2 clinical trials in patients with selected advanced solid tumors (NCT05256381, NCT05619172)."

Clinical • IO biomarker • Metastases • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL15

SOTIO Presents Data on SOT201 Immunocytokine and Other Programs at SITC Annual Meeting (Businesswire) - "SOTIO Biotech...announced it will be presenting new preclinical data at the Society for Immunotherapy of Cancer’s 38th Annual Meeting....Data to be presented include new preclinical results supporting the continued development of SOT201, a next-generation PD-1-inhibiting cytokine that SOTIO is progressing toward a planned first-in-human study in the second quarter of 2024....Additional poster presentations at the meeting will include preclinical data on the synergistic effects of SOTIO’s IL-15 superagonist in combination with CAR T-cell therapies, as well as data on SOTIO’s IL-15 superagonist nanrilkefusp alfa."

New trial • Preclinical • Oncology

SOTIO Provides Update on Interim Data from Clinical Trials of Nanrilkefusp Alfa (Businesswire) - "SOTIO Biotech, a clinical-stage immuno-oncology company owned by PPF Group, today announced it will discontinue the currently ongoing clinical trials of nanrilkefusp alfa as monotherapy and in combinations with pembrolizumab and cetuximab. Interim data from SOTIO’s clinical trials of nanrilkefusp alfa have shown insufficient efficacy to warrant further development in larger randomized trials in these specific indications and combinations. Interim data revealed no major safety issues in any of the trials....Based upon the interim data, effective immediately, enrollment in the AURELIO-03, AURELIO-04, and AURELIO-05 clinical trials will be stopped....SOTIO will continue to advance its immunocytokine platform including preclinical development of SOT201, a next-generation PD-1-inhibiting cytokine that is on track to enter Phase 1 clinical development in the second quarter of next year."

New P1 trial • Trial termination • Anal Carcinoma • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor

AURELIO-03: Study of SO-C101 and SO-C101 in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=200 | Active, not recruiting | Sponsor: SOTIO Biotech AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Anal Carcinoma • Biliary Cancer • Bladder Cancer • Breast Cancer • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Hypoglycemia • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Mesothelioma • Microsatellite Instability • Neuroendocrine Tumor • Neutropenia • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thymus Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer

AURELIO-05: A Study of SOT101 in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: SOTIO Biotech AG | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CRP • EGFR • KRAS

AURELIO-04: A phase 2, open-label, single-arm, multicenter study to determine the efficacy and safety of SOT101 in combination with pembrolizumab in patients with selected advanced solid tumors (SITC 2022) - P1, P2 | "Methods AURELIO-04 is a phase 2 single-arm study in: Non-small cell lung cancer after a CPI and/or platinum regimen, with no EGFR or ALK aberration Unresectable or metastatic MSI-H/dMMR colorectal cancer First-line cutaneous squamous cell carcinoma not curable by surgery or radiation and second-line after a CPI regimen Hepatocellular carcinoma after a CPI regimen Metastatic castrate-resistant prostate cancer (mCRPC) after docetaxel Ovarian cancer after a platinum regimen Main inclusion criteria are measurable disease as per RECIST 1.1, accessible tumor tissue, ECOG PS 0-1, adequate organ function, no prior IL-2 or IL-15 therapy. Exploratory analyses include immune and molecular biomarkers. Recruitment started in June 2022."

Clinical • Combination therapy • IO biomarker • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • ALK • CD8 • EGFR • IL15 • IL2 • MSI

[VIRTUAL] A multicenter open-label phase I/lb study of SO-C101 as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors (SITC 2020) - P1 | "The study will proceed to reach a RP2D in both monotherapy and combination with Pembrolizumab. Expansion of the study in selected indications is warranted."

Clinical • Combination therapy • Late-breaking abstract • Monotherapy • Oncology • Solid Tumor • CD8 • IL15 • IL2

[VIRTUAL] Pharmacodynamics and pharmacokinetics of SO-C101 in cynomolgus monkeys (SITC 2020) - P1 | "These data were used to determine the starting dose and subsequent dose escalation steps of SO-C101 in an ongoing Phase I clinical trial in patients with advanced solid tumors. Conclusions Since the potency of SO-C101 to activate NK and CD8+ T cells in vitro is equivalent between human and cynomolgus monkeys, these studies informed the dose and schedule selection for the ongoing Phase I clinical study (NCT04234113)."

PK/PD data • Oncology • Solid Tumor • CD8 • IL15

[VIRTUAL] Pharmacodynamics and pharmacokinetics of SO-C101 in cynomolgus monkeys (SITC 2020) - P1 | "These data were used to determine the starting dose and subsequent dose escalation steps of SO-C101 in an ongoing Phase I clinical trial in patients with advanced solid tumors. Conclusions Since the potency of SO-C101 to activate NK and CD8+ T cells in vitro is equivalent between human and cynomolgus monkeys, these studies informed the dose and schedule selection for the ongoing Phase I clinical study (NCT04234113)."

PK/PD data • Oncology • Solid Tumor • CD8 • IL15

SOT101, an IL-2/IL-15 Rβγ superagonist, in combination with pembrolizumab in patients with advanced solid tumors: Interim safety and efficacy results from the AURELIO-03 dose escalation trial (AACR 2022) - P1 | "SOT101 in combination with pembrolizumab showed a favorable safety profile. Highly promising efficacy signals were reported in ICB-naïve and ICB pre-treated patients, including ICB-resistant tumors."

Clinical • Combination therapy • Anal Carcinoma • Cervical Cancer • Colorectal Cancer • Endocrine Cancer • Gastric Cancer • Gastrointestinal Cancer • Liver Cancer • Lung Cancer • Melanoma • Mesothelioma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Thyroid Gland Carcinoma • IL15 • IL2

SOTIO Doses First Patient in AURELIO-05 Phase 2 Trial of Nanrilkefusp Alfa in Combination with Cetuximab (GlobeNewswire) - "SOTIO Biotech...announced today that the first patient was dosed in its Phase 2 AURELIO-05 combination trial of nanrilkefusp alfa (previously known as SOT101), an IL-15 superagonist, and cetuximab in patients with colorectal cancer....The Phase 2 AURELIO-05 trial (NCT05619172) is an open-label, single-arm, multicenter study to evaluate the efficacy and safety of nanrilkefusp alfa in combination with cetuximab in up to 52 patients with RAS wild-type colorectal cancer who are relapsed/refractory or intolerant to prior treatment with irinotecan- and oxaliplatin-containing chemotherapy."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of SOT101 in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: SOTIO Biotech AG

Combination therapy • New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CRP • EGFR • KRAS