Study of DF6215 in Patients with Advanced Solid Tumors

Key Inclusion Criteria * Male or female patients ≥ 18 years old. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * An estimated life expectancy of ≥ 3 months. * Adequate hematological function. * Normal pulmonary function. * Adequate hepatic function. * Adequate renal function. * Effective Contraception. * Additional Inclusion Criteria apply to each cohort. Key Exclusion Criteria * Patients receiving chemotherapy, radiotherapy (other than palliative bone-directed radiotherapy), major surgery, or receiving another systemic anticancer therapeutic agent within 28 days before the start of study drug(s) or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter. * Patients receiving any of the following concurrent anticancer treatments or investigational drugs within 28 days before the start of the study drug(s), or within 5 half-lives of the previous therapeutic agent (if known), whichever is shorter: * Cytoreductive therapy * Radiotherapy (except for palliative bone-directed radiotherapy) * Note: ≤ 2 weeks of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study drug. * Immune therapy * Cytokine therapy (except for erythropoietin) * Major surgery (excluding prior diagnostic biopsy) * Concurrent systemic therapy with steroids or other immunosuppressive agents. * Note that short-term administration of systemic steroids (eg, for allergic reactions or the management of irAEs) and physiologic dose steroids (≤ 10 mg prednisone, or equivalent) for those with treated brain metastases are allowed. Patients receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug(s) will be excluded. * Bisphosphonate or denosumab initiated within 14 days of the first dose of study drug(s) * Previous malignant disease, other than the target malignancies to be investigated in this study, within the last 3 years. Exceptions (eg, basal or squamous cell carcinoma of the skin, low grade prostate cancer \[Gleason score ≤ 6 and must be Stage I or II\], or cervical carcinoma in situ) may be considered on a case-by-case basis, in consultation with the Medical Monitor. * Any of the following cardiac abnormalities: * A clinically relevant abnormality on the electrocardiogram (ECG) * Clinically relevant coronary artery disease (CAD) or uncontrolled congestive heart failure * Medically uncontrolled angina pectoris * An implantable pacemaker or automatic implantable cardioverter-defibrillator * A history of risk factors for ventricular tachycardia, torsades de pointes, fainting, unexplained loss of consciousness, or convulsions * A history of heart failure, congestive heart failure, cardiomyopathy, uncontrolled hypokalemia, hypomagnesemia, or hypoglycemia; any evidence of conduction abnormality (eg, increased QRS complex) * Congenital long QT syndrome or a prolonged QTc mean on screening ECG * QTc \> 470 msec for women and \> 450 msec for men * History of myocardial infarction within 6 months before the first dose of study drug(s) * Received sotalol within 10 days of the first dose of study drug(s), or received a medication known to prolong the ECG QT interval within 14 days of the first dose of study drug(s) * A heart rate of \< 50 or \> 100 bpm at rest on screening ECG * Patients aged more than 50 years must have a normal cardiac stress test. * Patients with history of CAD must have a normal stress test (eg, thallium or technetium-99m sestamibi) and be cleared to participate in the study. * History of ocular/uveal melanoma or mucosal melanoma. * Primary tumor site of nasopharynx (any histology). * Patients with brain metastases are excluded, unless all of the following criteria are met: * CNS lesions are asymptomatic and previously treated * Patient does not require ongoing daily steroid treatment for replacement for adrenal insufficiency (except ≤ 10 mg prednisone \[or equivalent\]) for at least 14 days before the first dose of study drug * Imaging demonstrates stable disease 28 days after last treatment * Receipt of any organ transplant, including autologous or allogeneic stem-cell transplantation. * Patients must not have received aldesleukin or any other experimental IL-2 based drug, including intralesional administration. * Significant acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV) infection during the screening window, as well as historic positive for human immunodeficiency virus (HIV) or clinically significant active infections that render the patient ineligible for study treatment as determined by the treating investigator. * Patients with known HIV infection are excluded unless they meet the following criteria: * Must have CD4+ T-cell (CD4+) counts ≥ 350 cells/μL at the time of screening, and * Must have no history of AIDS-related opportunistic infections of HIV-associated conditions such as Kaposi sarcoma or multicentric Castleman's disease, and * Patients on antiretroviral therapy (ART) must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening and agree to continue ART throughout the study * Preexisting autoimmune disease (except vitiligo) needing treatment with systemic immunosuppressive agents for more than 28 days within the last 3 years, or clinically relevant immunodeficiencies (eg, dysgammaglobulinemia or congenital immunodeficiencies). Patients with a history of immune related endocrinopathies (eg, hypothyroidism, hyperthyroidism, and type 1 diabetes mellitus) that are stable on hormone replacement therapy are eligible for this study. * Patients with a known medical history of keratitis, ulcerative keratitis, or corneal perforation. * Patients with known history of neurologic conditions, cerebrovascular accident, or seizures. * Known severe hypersensitivity reactions to mAbs (≥ Grade 3 as defined by NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly controlled asthma). * Persisting toxicity related to a prior therapeutic agent \> Grade 1 as defined by NCI CTCAE v5.0 (however, ≤ Grade 2 alopecia, ≤ Grade 2 endocrinopathies, and ≤ Grade 2 sensory neuropathy are acceptable). * Patients in certain cohorts with prior anti-PD-1 and anti-PD-L1 treatment are eligible for the study, unless they have experienced any of the following: * Grade 3 or 4 treatment-related toxicity during an anti-PD-1 or anti-PD-L1 treatment (excluding Grade 3 or 4 immune-related endocrinopathies adequately controlled with hormone replacement therapy). * Grade 2 treatment-related toxicity that impacted either the lungs, the nervous system, or the cardiac system, during an anti-PD-1 or anti-PD-L1 treatment (patients with a history of Grade 2 peripheral neuropathy, or paresthesia, not related to anti-PD-1 or anti-PD-L1 treatments are eligible). * For combination basket cohorts: received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). * For combination basket cohorts: received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis. * Known alcohol or drug abuse. * Severe dyspnea at rest due to complications of advanced malignancy. * Requiring supplementary oxygen therapy. * All other significant diseases (eg, inflammatory bowel disease) which, in the opinion of the Investigator, might impair the patient's ability to participate. * Legal incapacity or limited legal capacity. * Unable to understand or give signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol. Examples include certain psychiatric conditions. * Patients who have received a live or live-attenuated vaccine within 30 days before the first dose of study drug. Administration of killed vaccines is allowed. * Pregnant or lactating. * Severe hypersensitivity (≥ Grade 3) to study drugs and/or any of their excipients. * Additional Exclusion Criteria apply to each cohort.