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

SOTIO

Status and phase: Active, not recruiting; Phase 1

Conditions: Anal Cancer; Small-cell Lung Cancer; Melanoma; Biliary Tract Cancer; Non Small Cell Lung Cancer; Ovarian Cancer; Microsatellite Instability High; Merkel Cell Carcinoma; Bladder Cancer; Gastric Cancer; Hepatocellular Carcinoma; Thyroid Cancer; Thymic Cancer; Mesothelioma; Triple Negative Breast Cancer; Renal Cell Carcinoma; Cervical Cancer; Skin Squamous Cell Carcinoma; Head and Neck Squamous Cell Carcinoma

Treatments: Drug: Pembrolizumab; Drug: Nanrilkefusp alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT04234113

2018-004334-15 (EudraCT Number)

AURELIO-03 (Other Identifier)

SC103

Details and patient eligibility

About

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

Full 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).

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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200 participants in 6 patient groups

Experimental: Part A (nanrilkefusp alfa monotherapy)

Experimental group

Description:

Drug: Nanrilkefusp alfa

Treatment:

Drug: Nanrilkefusp alfa

Experimental: Part B (nanrilkefusp alfa combined with pembrolizumab)

Experimental group

Description:

Drug: Nanrilkefusp alfa Drug: Pembrolizumab

Treatment:

Drug: Nanrilkefusp alfa

Drug: Pembrolizumab

Experimental: Part A1 (nanrilkefusp alfa divided dosing, monotherapy)

Experimental group

Description:

Drug: Nanrilkefusp alfa, twice a day as 2 divided doses (50%:50%)

Treatment:

Drug: Nanrilkefusp alfa

Experimental: Part B1 (nanrilkefusp alfa divided dosing, combined with pembrolizumab)

Experimental group

Description:

Drug: Nanrilkefusp alfa, twice a day as 2 divided doses (50%:50%) Drug: Pembrolizumab

Treatment:

Drug: Nanrilkefusp alfa

Drug: Pembrolizumab

Experimental: Part D (nanrilkefusp alfa monotherapy, expansion at the RP2D identified in Part A)

Experimental group

Description:

Drug: Nanrilkefusp alfa Indications: Relapsed/refractory advanced/metastatic renal cell carcinoma, relapsed/refractory advanced/metastatic skin squamous-cell carcinoma, relapsed/refractory advanced/metastatic melanoma

Treatment:

Drug: Nanrilkefusp alfa

Part D1 (nanrilkefusp alfa divided dosing, monotherapy, expansion at the RP2D identified in Part A1)

Experimental group

Description:

Drug: Nanrilkefusp alfa, twice a day as 2 divided doses (50%:50%) Indications: Relapsed/refractory advanced/metastatic renal cell carcinoma, relapsed/refractory advanced/metastatic skin squamous-cell carcinoma, relapsed/refractory advanced/metastatic melanoma

Treatment:

Drug: Nanrilkefusp alfa