The purpose of this First-in-Human, open-label, dose escalation and expansion study is to
assess the initial safety and efficacy profile of ANV419 intravenous infusion in patients
with advanced solid tumours. Phase 1 will evaluate the safety and tolerability of ANV419
alone and to determine a suitable dose for Phase 2 development. Phase 2 will evaluate the
preliminary efficacy and, the safest and best dose of ANV419 when used alone or together with
established cancer treatment.
- Ability of the patient or legal guardian to understand the purpose of the study,
provide signed and dated informed consent from the patient prior to performing any
protocol-related procedures (including Screening evaluations), and be able and willing
to comply with the study procedures.
- Male or female aged ≥ 18 years.
- Advanced solid tumors with evidence of progressive disease as per RECIST no longer
than 3 months before Informed Consent form (ICF) signature, without any subsequent
curative intent treatment.
- Parts A and B only: Histologically confirmed relapsed/refractory advanced solid tumor,
progressing after at least one line of treatment for advanced or metastatic disease.
- Parts C and D only: Histologically confirmed solid tumors, relapsed post or were
refractory to at least one line of treatment for advanced disease. BRAF mutant
melanoma must have progressed to BRAF + MEK inhibitor.
- Parts C and D only: Radiologically measurable disease as per RECIST v1.1.
- No additional established line of on-label treatment is available or there is a
contraindication for the indicated labelled therapies as deemed by the Investigator.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
- Adequate pulmonary, cardiovascular, hematological, liver and renal function, per
- All acute toxic effects, of any prior anticancer therapy (e.g., radiotherapy,
chemotherapy, or surgical procedures) must have resolved to CTCAE v5.0 grade ≤1
(except alopecia [any grade] or asthenia [up to grade 2 allowed]).
- Negative serum pregnancy test within 7 days prior to study treatment in women of
childbearing potential and women <12 months after menopause.
- For women who are not postmenopausal and have not undergone surgical sterilization:
agreement to remain abstinent or use two adequate highly effective non-hormonal
methods of contraception, including at least one method with a failure rate of <1 %
per year, during the treatment period and until 6 months after the last dose of study
- For men: agreement to remain abstinent or use contraceptive measures and agreement to
refrain from donating sperm during the treatment period and for at least 6 months
after the last dose of study treatment.
- Availability and willingness of patients to obtain a baseline and on treatment biopsy
of the tumor. Available archived biopsies (frozen or formalin fixed) may serve as
baseline specimens, in patients who have residual tumor masses which can only be
accessed with significant risk
- Symptomatic central nervous system (CNS) metastases. Definitively treated CNS
metastases (e.g., radiotherapy) stable for at least 6 weeks prior to Day 1 of study
drug administration are acceptable.
- Participants with an active second malignancy. Patients with precancerous lesions,
concomitant early stages of prostate or breast cancer not requiring active treatment
(past conditions currently resolved > 3 years prior to Screening are also acceptable),
and squamous cell carcinoma of the skin not requiring systemic treatment are
- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results, including uncontrolled
diabetes mellitus, history of relevant pulmonary disorders, (e.g., severe
bronchospasm, obstructive pulmonary disease), hyperthyroidism due to thyroiditis and
known autoimmune diseases or other disease with ongoing fibrosis. Stable vitiligo,
autoimmune thyroiditis, and preexisting treated type 1 diabetes are acceptable and are
not exclusion criteria.
- Significant cardiovascular/cerebrovascular disease, including myocardial infarction or
transient ischemic attack (TIA) within 6 months prior to Day 1 of study drug
- Active or uncontrolled infections requiring systemic antibiotics within one week (7
days) preceding Day 1 of treatment
- Hemoglobin (Hb) <9 g/dL, transfusion of red blood cells allowed to reach threshold
- Neutrophils <1500 /mm3.
- Platelets <75000/mm3.
- Liver: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5x upper
limit of normal (ULN), total bilirubin > 1.5xULN (in documented Gilbert's syndrome >
3mg/dl) however, if caused by liver metastasis as judged by the Investigator and
Sponsor AST and ALT >5xULN.
- International normalized ratio (INR) >1.5xULN.
- Serum creatinine < 1.5 mg/dL or a measured creatinine clearance ≥ 50 mL/min using the
- Known replicating human immunodeficiency virus (HIV) or known active (replicative)
hepatitis B virus or hepatitis C virus infection. Patients with treated
non-replicative disease are acceptable.
- Positivity for coronavirus disease 2019 (COVID-19) by naso-pharyngeal swab test. Known
serologic conversion is not an exclusion criterion.
- Evidence of hepatic cirrhosis with Child-Pugh score C.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding > Grade 2 that give reasonable suspicion of a disease or condition
that would contraindicate the use of an investigational drug.
- Major surgery or significant traumatic injury <28 days prior to the first ANV419
infusion (excluding biopsies) or anticipation of the need for major surgery during
- Severe altered mental status.
- Pregnant or breastfeeding women.
- Known hypersensitivity to any of the components of ANV419 or its formulation.
- Concurrent therapy with any other investigational drug within one month prior to Day 1
of study drug administration.
- Active untreated immune-related endocrinopathies untreatable with replacement. Prior
immune related toxicities > Grade 3 after treatment with immunostimulatory drugs
(e.g., colitis, neuropathy) that have not completely resolved.
- Chronic treatment with systemic immunosuppressive medications above 10 mg/day
prednisolone equivalent for any reason