AMT-253 in Patients With Selected Advanced Solid Tumours

Key Inclusion Criteria:

• Patients must be willing and able to sign the ICF, and to adhere to the study visitschedule and other protocol requirements.

• Age ≥18 years (at the time consent is obtained).

• Patients who have undergone at least one systemic therapy and have radiologically orclinically determined progressive disease during or after most recent line oftherapy, and for whom no further standard therapy is available, or who areintolerable to standard therapy.

• Patients must have at least one measurable lesion as per RECIST version 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Life expectancy ≥ 3 months.

• Patients must have adequate organ function.

• Women of child bearing potential (WCBP), defined as a sexually mature woman who hasnot undergone surgical sterilization or who has not been naturally postmenopausalfor at least 12 consecutive months (i.e., who has had menses any time in thepreceding 12 consecutive months) must agree to use two effective contraceptivemethods (examples include oral, parenteral, or implantable hormonal contraceptive,intra-uterine device, barrier contraceptive with spermicide, partner's latex condomor vasectomy) while on study treatment and for at least twelve weeks after the lastdose of the IMP.

• WCBP must have a negative serum pregnancy test within 7 days prior to first dose ofthe IMP.

• Male patients must agree to use a latex condom, even if they had a successfulvasectomy, while on study treatment and for at least twelve weeks after the lastdose of the IMP.

• Male patients must agree not to donate sperm, and female patients must agree not todonate eggs, while on study treatment and for at least 12 weeks after the last doseof the IMP.

• Availability of tumor tissue sample (either an archival specimen or a fresh biopsymaterial) at screening.

Key Exclusion Criteria:

• Central nervous system (CNS) metastasis.

• Active or chronic skin disorder requiring systemic therapy.

• History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.

• Active ocular conditions requiring treatment or close monitoring, including, but notlimited to: macular degeneration, papilledema, active diabetic retinopathy withmacular oedema, wet age-related macular degeneration requiring intravitrealinjections, or uncontrolled glaucoma.

• Persistent toxicities from previous systemic anti-neoplastic treatments of Grade >1.

• Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever isshorter, prior to first dose of the IMP.

• Radiotherapy to lung field at a total radiation dose of ≥20 Gy within 6 months,wide-field radiotherapy (e.g., > 30% of marrow-bearing bones) within 28 days.

• Major surgery (not including placement of vascular access device or tumor biopsies)within 28 days prior to first dose of the IMP, or no recovery from side effects ofsuch intervention.

• Significant cardiac disease, such as recent (within six months prior to first doseof the IMP) myocardial infarction or acute coronary syndromes (including unstableangina pectoris), congestive heart failure (New York Heart Association class III orIV), uncontrolled hypertension, uncontrolled cardiac arrhythmias.

• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis thatrequired steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis (e.g.,idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis,idiopathic pneumonitis, etc.).

• History of thromboembolic or cerebrovascular events, including transient ischemicattacks, cerebrovascular accidents, deep vein thrombosis, or pulmonary emboli withinsix months prior to first dose of the IMP.

• Acute and/or clinically significant bacterial, fungal or viral infection includinghepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV).

• Administration of a live vaccine within 28 days prior to the administration of thefirst dose of the IMP.

• Patients requiring concurrent treatment of strong inhibitors or inducers ofcytochrome P450 3A4 or 1A2 enzyme (CYP3A4 or CYP1A2) within 2 weeks prior to thefirst dose and during the study treatment.

• Patient who has active graft versus host disease, or diagnosis of immunodeficiency,or has an active autoimmune disease or other conditions that require systemicsteroid therapy, i.e. > 10 mg daily prednisone equivalents within 14 days prior tothe administration of the first dose; the use of short-course systemiccorticosteroids (≤ 7 days) is permitted, with a wash-out period of 1 week prior tothe administration of the first dose of the IMP.

• Known or suspected severe allergy/hypersensitivity (resulting in treatmentdiscontinuation) to monoclonal antibodies.

• Known or suspected intolerance to the components of the IMP.

• Concurrent participation in another investigational therapeutic clinical trial.

• Patients with known active alcohol or drug abuse.

• Pregnant or breast-feeding females.

• Mental or medical conditions that prevent the patient from giving informed consentor complying with the trial or other severe acute or chronic medical or psychiatricconditions or laboratory abnormality that may increase the risk associated with thestudy participation or the IMP administration or may interfere with theinterpretation of study results and, in the judgment of the investigator, would makethe patient inappropriate for enrolment in this study.

• Prior history of malignancy other than inclusion diagnosis within five years priorto first dose of the IMP.

Note: Other protocol defined Inclusion/Exclusion criteria apply.