AB821 for the Treatment of Unresectable or Metastatic Melanoma or other Recurrent, Locally Advanced, or Metastatic Solid Tumors

Inclusion Criteria

• ≥ 18 years at the time consent is signed
• Ability to provide written informed consent for the study
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Participants of childbearing potential must not be pregnant at enrollment and agree to comply with contraception requirements. Participants with partners of childbearing potential must also comply with contraception requirements
• Absolute neutrophil count (ANC) > 1500/µl (within seven days prior to the start of the study treatment [i.e., Cycle 1 Day 1 (C1D1)])
• Platelet count > 100,000 (within seven days prior to the start of the study treatment [i.e., Cycle 1 Day 1 (C1D1)])
• Hemoglobin (Hb) > 9 g/dl (within seven days prior to the start of the study treatment [i.e., Cycle 1 Day 1 (C1D1)])
• Calculated creatinine clearance ≥ 50 mL/min (within seven days prior to the start of the study treatment [i.e., Cycle 1 Day 1 (C1D1)])
• Total bilirubin (bili) ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin > 1.5 x ULN (within seven days prior to the start of the study treatment [i.e., Cycle 1 Day 1 (C1D1)])
• Prothrombin time (PT) international normalized ratio (INR) > 1.5 x ULN unless on anticoagulation (within seven days prior to the start of the study treatment [i.e., Cycle 1 Day 1 (C1D1)])
• Albumin > 3g/dl (within seven days prior to the start of the study treatment [i.e., Cycle 1 Day 1 (C1D1)])
• Life expectancy of ≥ 12 weeks, per treating investigator's judgment
• For melanoma participants: Participants with unresectable or metastatic melanoma that have progressed on or after PD-1/PD-L1 checkpoint blockade (alone or with either CTLA-4 or LAG-3 checkpoint blockade) * Note: Participants known to be BRAF V600 mutation-positive; prior therapy with BRAF ± MEK inhibitor is at the treating investigator’s discretion
• For other tumor types: Must have a recurrent histologically or cytologically proven metastatic or locally advanced solid tumor (non-small cell lung cancer [NSCLC], renal cell carcinoma [RCC], Merkel-cell carcinoma, bladder cancer, or squamous cell carcinoma of the head and neck [SCCHN]), meeting each of the following: * Tumor that is not amenable to curative treatment with surgery or radiation * Tumor for which immune checkpoint inhibitors form part of standard-of-care therapy * Participant has received at least one prior line of systemic anticancer therapy in the recurrent or metastatic setting
• Has measurable disease per RECIST v1.1 as assessed by the local site investigator/radiology

Exclusion Criteria

• Has a diagnosis of immunodeficiency
• Prior stem cell, bone marrow, or organ transplant
• Known history of HIV infection. No HIV testing is required unless mandated by local health authority
• History of hepatitis B virus (HBV) (defined as HBV surface antigen reactive) or active hepatitis C virus (HCV)
• Active autoimmune disease (non-immunotherapy induced conditions) that has required systemic treatment in the past two years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic immune-suppressive treatment and is allowed
• Active grade ≥ 2 diarrhea or enterocolitis
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Individuals with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least two weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment)
• Any other current or previous malignancy within the previous three years except neoplasms that, in the opinion of the treating investigator and with the agreement of the sponsor-investigator, will not interfere with study-specific endpoints, e.g. basal cell carcinoma, localized tumors that have been fully excised with curative intent and no evidence of recurrence or metastasis, prostate cancer that is asymptomatic and does not require therapy other than anti-androgen therapy
• Participant is a regular user, as determined by treating investigator judgment (including recreational use), of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing the informed consent form (ICF)
• Has clinically significant heart disease that affects normal activities, including, unstable angina, or history of congestive heart failure (New York Heart Association class II-IV)
• History of acute myocardial infarction within the last six months
• Has a history of new or worsening thrombosis (deep vein thrombosis [DVT]/pulmonary embolism [PE], other thrombo-embolic disease) within the last six months
• Has a mean Fridericia’s formula–corrected QT interval (QTcF) value of > 470 ms
• Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the individuals’ participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator
• Has an active infection, requiring systemic therapy
• Has had a severe hypersensitivity reaction to any components of the study treatment or any of their excipients
• Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior the first dose of study treatment
• Has received more than five prior lines of systemic treatment in the recurrent/metastatic setting
• Has received prior radiotherapy within two weeks of start of study treatment or has had a history of radiation pneumonitis * Note: Participants must have recovered from all radiation related toxicities and not require corticosteroids. A minimum of 1 week is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease
• Has a history of grade 3-4 autoimmune myocarditis or a history of Guillain Barre syndrome
• History of congestive heart failure with an ejection fraction < 40%
• Participant with NSCLC only: Has received radiation therapy to the lung that is > 30 Gy within six months of the first dose of study treatment
• Has received previous IL-21 based therapy or prior therapy with AB248
• Prior systemic anticancer therapy including investigational agents within four weeks or, if shorter, within five half-lives prior to first dose of study treatment * Note: Individuals must have recovered from all adverse events (AEs) due to previous therapies to grade ≤ 1 or baseline. Participants with grade ≤ 2 neuropathy from chemotherapy or targeted therapy are eligible. Participants with endocrine related AEs grade ≤ 2 requiring treatment or hormone replacement are eligible * Note: Bisphosphonates, denosumab (or biosimilars), or other monoclonal antibody treatment for the purpose of supportive care for bone metastases are permitted
• Major surgery from which the participant has not fully recovered
• Has received a live or live attenuated vaccine within 30 days
• Current use of any prohibited concomitant medications
• A participant of childbearing potential who has a positive serum pregnancy test within 14 days prior to treatment