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

Phase 1TerminatedNCT04234113

SOTIO Biotech AG115 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

115

Conditions

Thyroid Cancer Renal Cell Carcinoma Non Small Cell Lung Cancer

Interventions

Nanrilkefusp alfaDRUG

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

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Patients with selected histologically or cytologically confirmed advanced and/or metastatic solid tumors who are refractory to or intolerant of existing therapies known to provide clinical benefit for their condition. * ECOG performance score 0-1. Patients with ECOG 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 * 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 Exclusion criteria: * 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

Locations (12)

Yale Cancer Center

New Haven, Connecticut, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Masarykův Onkologický Ústav Brno Klinika komplexní onkologické péče

Brno, Czechia, Czechia

Centre Léon Bérard

Lyon, France, France

Institut Gustave Roussy

Paris, France, France

Institut Claudius Regaud

Toulouse, France, France

Hôpitaux Universitaires de Marseille Timone

Marseille, France

Hopital Saint Louis

Paris, France

Institut de Cancerologie de L'Ouest

Saint-Herblain, France

...and 2 more locations

Outcomes

Primary Outcomes

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

Time frame: Through Cycle 1 (21 days)

Number of Participants With Adverse Events (AEs)

Nanrilkefusp alfa related only