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

Centre Léon Bérard

Lyon, France

Hôpitaux Universitaires de Marseille Timone

Marseille, France

Hopital Saint Louis

Paris, France

Institut Gustave Roussy

Paris, France

Institut de Cancerologie de L'Ouest

Saint-Herblain, France

Institut Claudius Regaud

Toulouse, France

...and 2 more locations

Outcomes

Primary Outcomes

Part A: Number of participants with dose-limiting toxicities (DLTs)

Adverse events (AEs) as per NCI CTCAE version 5.0: * Grade 5 not related to disease progression or other causes * Grade ≥3 non-hematologic toxicity; exceptions: grade 3 nausea, vomiting or diarrhea controlled in 72 hours; grade 3 fatigue \<5 days; grade ≥3 correctable electrolyte abnormalities \<72 hours and no clinical complications; grade ≥3 amylase or lipase without clinical pancreatitis * Hy's law cases * Grade 3 AST or ALT or grade 3 bilirubinemia \>5 days * Hematologic DLTs: * Grade 4 neutropenia or thrombocytopenia \>7 days * Febrile neutropenia * Grade ≥3 thrombocytopenia with bleeding * Grade 4 immune-related AEs * Grade 3 or 4 non-infectious pneumonitis * Grade 3 immune-related AEs, excluding colitis, hepatitis, and pneumonitis, not downgrading to grade ≤2 in 3 days despite maximal supportive care including systemic corticosteroids or to grade 1 or baseline in 14 days * Grade 2 pneumonitis not downgrading to grade 1 in 3 days * Grade 3 colitis

Time frame: Through Cycle 1 (21 days)

Part A1: Number of participants with DLTs

AEs as per NCI CTCAE version 5.0: * Grade 5 not related to disease progression or other causes * Grade ≥3 non-hematologic toxicity; exceptions: grade 3 nausea, vomiting or diarrhea controlled in 72 hours; grade 3 fatigue \<5 days; grade ≥3 correctable electrolyte abnormalities \<72 hours and no clinical complications; grade ≥3 amylase or lipase without clinical pancreatitis * Hy's law cases * Grade 3 AST or ALT or grade 3 bilirubinemia \>5 days * Hematologic DLTs: * Grade 4 neutropenia or thrombocytopenia \>7 days * Febrile neutropenia * Grade ≥3 thrombocytopenia with bleeding * Grade 4 immune-related AEs * Grade 3 or 4 non-infectious pneumonitis * Grade 3 immune-related AEs, excluding colitis, hepatitis, and pneumonitis, not downgrading to grade ≤2 in 3 days despite maximal supportive care including systemic corticosteroids or to grade 1 or baseline in 14 days * Grade 2 pneumonitis not downgrading to grade 1 in 3 days * Grade 3 colitis

Time frame: Through Cycle 1 (21 days)

Part B: Number of participants with DLTs

Time frame: Through Cycle 1 (21 days)

Part B1: Number of participants with DLTs

Time frame: Through Cycle 1 (21 days)

Part A: Number of participants with AEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part A1: Number of participants with AEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part B: Number of participants with AEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part B1: Number of participants with AEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part D: Number of participants with AEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part A: Number of participants with serious AEs (SAEs)

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part A1: Number of participants with SAEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part B: Number of participants with SAEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part B1: Number of participants with SAEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part D: Number of participants with SAEs

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part A: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part A1: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part B: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part B1: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part D: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa

Nanrilkefusp alfa related only

Time frame: Day 1 up to approximately 3 years

Part A: Number of participants who died

Nanrilkefusp alfa-related deaths only

Time frame: Day 1 up to approximately 3 years

Part A1: Number of participants who died

Nanrilkefusp alfa-related deaths only

Time frame: Day 1 up to approximately 3 years

Part B: Number of participants who died

Nanrilkefusp alfa-related deaths only

Time frame: Day 1 up to approximately 3 years

Part B1: Number of participants who died

Nanrilkefusp alfa-related deaths only

Time frame: Day 1 up to approximately 3 years

Part D: Number of participants who died

Nanrilkefusp alfa-related deaths only

Time frame: Day 1 up to approximately 3 years

Part A: Number of participants with nanrilkefusp alfa-related clinical laboratory test abnormalities (coagulation; hematology; clinical chemistry; urinalysis; thyroid and cardiac function)

The following laboratory parameters will be 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

Time frame: Day 1 up to approximately 3 years

Part A1: 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 3 years

Part B: 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 3 years

Part B1: 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 3 years

Part D: 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 3 years

Secondary Outcomes

Part A: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Time frame: Cycle 1 Day 1, 1 hour (+/-15 minutes)

Part A1: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Time frame: Cycle 1 Day 1, 1 hour (+/-15 minutes)

Part B: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Time frame: Cycle 1 Day 1, 1 hour (+/-15 minutes)

Part D: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Time frame: Cycle 1 Day 1, 1 hour (+/-15 minutes)

Part A: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Time frame: Cycle 1 Day 1, 4 hours (+/-15 minutes)

Part A1: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Time frame: Cycle 1 Day 1, 4 hours (+/-15 minutes)

Part B: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Time frame: Cycle 1 Day 1, 4 hours (+/-15 minutes)

Part D: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)

After 12 μg/kg nanrilkefusp alfa administration

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: Cycle 1 Day 1, 4 hours (+/-15 minutes)

Part A: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A1: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part B: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part D: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A1: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part B: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part D: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A1: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part B: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part D: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A1: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part B: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part D: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A1: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part B: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part D: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A1: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part B: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part D: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa

At 12 μg/kg nanrilkefusp alfa

Time frame: Day 6 of Cycle 1

Part A: Objective response rate (ORR)

Based on investigator review of radiographic images according to Response Evaluation Criteria In Solid Tumors for immune-based therapeutics (iRECIST)

Time frame: Day 1 up to approximately 3 years

Part A1: ORR

Based on investigator review of radiographic images according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part B: ORR

Based on investigator review of radiographic images according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part D: ORR

Based on investigator review of radiographic images according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part A: Duration of response (DoR)

DoR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part A1: DoR

DoR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part B: DoR

DoR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part D: DoR

DoR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part A: Clinical benefit rate (CBR)

CBR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part A1: CBR

CBR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part B: CBR

CBR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part D: CBR

CBR according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part A: Progression-free survival (PFS)

PFS according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part A1: PFS

PFS according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part B: PFS

PFS according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part D: PFS

PFS according to iRECIST

Time frame: Day 1 up to approximately 3 years

Part A: Number of participants with anti-drug antibodies (ADAs) at the end of treatment

Against nanrilkefusp alfa

Time frame: End of treatment with nanrilkefusp alfa

Part A1: Number of participants with ADAs at the end of treatment

Against nanrilkefusp alfa

Time frame: End of treatment with nanrilkefusp alfa

Part B: Number of participants with ADAs at the end of treatment

Against nanrilkefusp alfa

Time frame: End of treatment with nanrilkefusp alfa

Part B1: Number of participants with ADAs at the end of treatment

Against nanrilkefusp alfa

Time frame: End of treatment with nanrilkefusp alfa

Part D: Number of participants with ADAs at the end of treatment

Against nanrilkefusp alfa

Time frame: End of treatment with nanrilkefusp alfa