First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1046 in Subjects With Malignant Solid Tumors - GCT1046-01

Studio Clinico

Patologia: Carcinoma della vescica, Neoplasie della mammella, Neoplasie del polmone, Tumori dell’utero, Tumori della testa e del collo, Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, II

Linee di trattamento: Non applicabile

Criteri di inclusione: 

For Dose Escalation:
- Have a histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy

For Expansion:
- Have histologically or cytological confirmed diagnosis of relapsed or refractory, advanced and/or metastatic NSCLC, EC, UC, TNBC, SCCHN, or cervical cancer who are not anymore candidates for standard therapy

For Both Dose Escalation and Expansion:
- Have measurable disease according to RECIST 1.1
- Have Eastern Cooperative Oncology Group (ECOG) 0-1
- Have an acceptable hematological status
- Have acceptable liver function
- Have an acceptable coagulation status
- Have acceptable renal function

Criteri di esclusione: 

- Have uncontrolled intercurrent illness, including but not limited to:
    - Ongoing or active infection requiring intravenous treatment with antiinfective therapy
    - Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia
    - Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, despite optimal medical management
    - Ongoing or recent evidence of autoimmune disease
    - History of irAEs that led to prior checkpoint treatment discontinuation
    - Prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade
    - History of chronic liver disease or evidence of hepatic cirrhosis
    - History of non-infectious pneumonitis that has required steroids or currently has pneumonitis
    - History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1046
    - Serious, non-healing wound, skin ulcer (of any grade), or bone fracture
- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke
- Prior therapy:
    - Radiotherapy: Radiotherapy within 14 days prior to first GEN1046 administration. Palliative radiotherapy will be allowed.
    - Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1046 administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab
- Toxicities from previous anti-cancer therapies that have not adequately resolved.

Schema di trattamento: 

GEN1046 will be administered intravenously once every 21 days.
GEN1046 in combination with docetaxel (in a single expansion cohort) will be administered intravenously once every 21 days.

Trattamento sperimentale: 

GEN1046

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- Dose limiting toxicity (DLT) [ Time Frame: DLTs are assessed during the first cycle (21 days) in each cohort] ]
    to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

- Adverse events [ Time Frame: AEs are collected throughout the study and up to 2 months after last subject last treatment ]
    Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0

- Safety laboratory parameters (hematology, biochemistry, coagulation, endocrines) [ Time Frame: Safety laboratory data are collected throughout the study and up to 2 months after last subject last treatment ]
    Laboratory parameters graded by CTCAE v5.0

Note generali: 

Linea di trattamento: metastatica

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2018-003402-63

Data di inserimento: 28.07.2021

Promotore

Genmab

Principal Investigator ITALIA

Istituto Nazionale Tumori IRCCS - Fondazione Pascale, Napoli

Riferimento: Dr. Paolo A. Ascierto

Telefono: 0815903236

Email: p.ascierto@istitutotumori.na.it

Localita: Napoli