Inclusion Criteria:
- - 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.
- - Histologically confirmed relapsed/refractory advanced solid tumor, progressing after
at least one line of treatment for advanced or metastatic disease, or for multiple
myeloma, progressing during or after at least three lines of treatment including an.
- - IMiD, a proteasome inhibitor and a aCD38 agent.
- - Patients with multiple myeloma (MM) must have measurable disease (non-secretory MM
must have measurable active lesions in PET) and have had evidence of a previous
response (PR or better) to lenalidomide or daratumumab according to IMWG2016.
- - 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
Investigator judgment.
- - 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 fatigue [up to grade 2 allowed]).
- - Negative serum pregnancy test at screening and a negative (urine or serum) pregnancy
test within 7 days prior to study day 1 in women of childbearing potential and women
<12 months after menopause.
- - Women who are not postmenopausal and who have not undergone surgical sterilization:
must agree to use highly effective methods of contraception during the treatment
period and until 6 months after the last dose of study treatment.
They must also agree
to not donate eggs (ova, oocytes) during the same timeframe.
- - All men with childbearing potential partners must agree to use highly effective
methods of contraception and barrier contraception (condom) during the treatment
period and for 6 months after the last dose of study treatment.
They must also agree
to not donate sperm during the same timeframe.
- - 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.
Exclusion Criteria:
- - 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
acceptable.
- - 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
administration.
- - 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
target.
- - Neutrophils <1500 /mm3.
- - Liver: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5xULN, if
due to liver metastasis or primary liver cancer, AST or ALT >5x ULN.
- - Total bilirubin > upper limit of normal (ULN) (in documented Gilbert's syndrome,
direct bilirubin > ULN).
- - International normalized ratio (INR) >1.5xULN.
- - Serum creatinine > ULN and estimated creatinine clearance < 50 mL/min using the
Cockcroft-Gault formula.
- - Confirmed replicating human immunodeficiency virus (HIV) or confirmed 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
study treatment.
- - 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.
