Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

Selected Inclusion Criteria:

• Patients must have measurable disease as per RECIST v1.1 criteria and documented byCT and/or MRI

• Part 2 includes but is not limited to:

• Cutaneous melanoma that is either locally unresectable or metastatic:

• BRAF wild type: progressed after receiving PD-1 containing therapy with orwithout an anti-CTLA-4

• BRAF mutation: patients who refused BRAF+MEK inhibitor

• Must have objective progression after receiving at least two cycles of priordoublet therapy (anti-PD-1/anti-CTLA-4 or anti-PD-1/anti-LAG-3)

• Radiographic progression ≥ 4 weeks prior to the first dose of study drug torule out late response to most recent therapy. The requirement for documentedradiologic progression may be waived after review by Medical Monitor (e.g., inthe case of progression beyond 12 weeks after starting a doublet)

• LDH ≤ 2.5 x ULN

• NSCLC: Unresectable locally advanced or metastatic PD-L1-positive (tumor proportionscore [TPS] ≥ 1%) NSCLC not harboring an activating EGFR mutation or ALKrearrangement and has progressed during or following treatment with an anti-PDx withor without platinum-based chemotherapy

• Part 3: NSCLC as described above

• Part 4: cutaneous melanoma

• Unresectable locally advanced or metastatic cutaneous melanoma that hasprogressed during or following treatment with an anti-PDx (unless ineligiblefor anti-PDx therapy)

• Patients with BRAF mutations must either be ineligible for or have refused aBRAF+MEK inhibitor

• Must have objective progression after receiving at least two cycles of priordoublet therapy (anti-PD-1/anti-CTLA-4 or anti-PD-1/anti-LAG-3).

• Radiographic progression ≥ 4 weeks prior to the first dose of study drug torule out late response to most recent therapy. The requirement for documentedradiologic progression may be waived after review by Medical Monitor (e.g., inthe case of progression beyond 12 weeks after starting a doublet)

• LDH ≤ 2.5 x ULN

• Female patients of childbearing potential must have a negative serum or urinepregnancy test performed within 72 hours prior to the initiation of study drugadministration. Female patients of childbearing potential must be willing to use twoforms of contraception throughout the study, starting with Screening through 60 daysafter the last dose of study drug (or 5 months after the last dose of study drug forpatients receiving nivolumab). Abstinence is acceptable if this is the establishedand the preferred contraception method for the patient

• Male patients with partners of childbearing potential must use barrier contraceptionfrom the time of consent through 60 days after discontinuation of study drug andmust not donate sperm during this period. In addition, male patients should havetheir partners use contraception (as documented for female patients) for the sameperiod of time

• Patients who have previously received an immune checkpoint inhibitor (e.g.,anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have checkpointinhibitor immune-related toxicity resolved to either Grade ≤ 1 or baseline (prior tothe checkpoint inhibitor) to be eligible for enrollment. Patients who experiencedprevious checkpoint inhibitor-related hypothyroidism are eligible for the studyregardless of grade resolution if well controlled on thyroid hormone replacementtherapy

• Symptomatic central nervous system (CNS) metastases must have been treated, beasymptomatic for ≥ 14 days, and meet the following at the time of enrollment:

• No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg prednisone/day or equivalent)

• No concurrent leptomeningeal disease or cord compression

Exclusion Criteria:

• Patients with a history of known autoimmune disease with exceptions of

• Vitiligo

• Psoriasis, atopic dermatitis, or other autoimmune skin condition not requiringsystemic treatment

• History of Graves' disease in patients now euthyroid for > 4 weeks

• Hypothyroidism managed by thyroid hormone replacement

• Alopecia

• Arthritis managed without systemic therapy beyond oral nonsteroidal anti-inflammatory drugs

• Major surgery or traumatic injury within 3 weeks before first dose of AU-007

• Unhealed wounds from surgery or injury

• Treatment with > 10 mg per day of prednisone (or equivalent) or otherimmune-suppressive drugs within the 7 days prior to the initiation of study drug.Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed

• Prior anti-cancer therapy before the planned start of AU-007 as follows:

• Not recovered to baseline from toxicity of prior systemic cancer therapy(ies).

• Not recovered from toxicity of radiotherapy.

• Concurrent use of hormones either to maintain castrate levels of testosteronein patients with castration-sensitive prostate cancer or for non-cancer-relatedconditions (e.g., insulin for diabetes, hormone replacement therapy) isacceptable. Bisphosphonates are permitted.

• Patients who have experienced serious adverse events during prior IL-2 therapy (including but not limited to bowel perforation, gastrointestinal bleeding,arrythmias, myocardial infarction, repetitive seizures).

• Inflammatory process that has not resolved for ≥ 4 weeks from the date of firststudy dose. Patients with chronic low-grade inflammatory processes such asradiation-induced pneumonitis are excluded regardless of duration

• Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions includenon-melanoma locally advanced skin cancer, cervical carcinoma in situ, localizedprostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancyconsidered to be indolent and never required therapy, with the exception of indolentlymphomas