Clinical Trial Finder

Inclusion Criteria

Key Inclusion Criteria:

* Measurable disease per RECIST v1.1. For Cohort G participants must have at least 1 measurable lesion, and for Part 3 (Cohorts E, F and H) participants must have at least 2 measurable lesions to safely perform mandatory pre & on-treatment biopsy.
* Life expectancy greater than or equal to 12 weeks.
* For Part 2 exclusively: While it is highly preferred to enroll subjects who are naïve to PD-1 inhibitors into a Part 2 dose escalation cohort, this is not an enrollment requirement. However, subjects who enroll into a Part 2 safety expansion cohort must be naïve to PD-1 inhibitors. If such subject is unable to meet this requirement but otherwise remains a good candidate for study enrollment, the Investigator should discuss with the Sponsor whether the subject may be enrolled.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate cardiovascular, hematological, liver, and renal function.
* Histologically or cytologically confirmed diagnosis of advanced and/or metastatic solid tumors with at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the Investigator.

* Caution: Cohort D only patients with KRAS mutant colon cancer have not typically benefitted from the addition of cetuximab in earlier lines of therapy.
* Caution: Cohorts E & F enrollment will include only patients with tumors for which anti-PD(L)1 as single agent or in combination treatments are approved.
* Caution: For Cohort H, the participant must have received at least one prior line of therapy for metastatic melanoma and/or does not have any standard of care (SoC) treatment option or participant declines or is intolerant to be treated with SoC treatment.
* Subjects with advanced or metastatic solid tumors who have refused SoC; or for whom no reasonable SoC exists that would confer clinical benefit; or for whom standard therapy is intolerable, not effective, or not accessible.
* Prior anti-cancer therapy is allowed as long as any treatment related toxicity is resolved to an appropriate level.
* Females of childbearing potential and men who are not surgically sterile must agree to use medically-accepted method of birth control during the study and for at least7 days (for Cohorts A, B, G and H), at least 2 months (for Cohort D), or at least 4 months (for Cohorts C, E and F) for females, and for at least 3 days for males [corresponding to the time needed to eliminate study intervention] after the last dose of study intervention.
* [Females] Negative serum pregnancy test within 7 days prior to initiating study treatment in premenopausal women and women less than 12 months after menopause.
* [Males] Agreement to refrain from donating or banking sperm during the treatment period and for at least 3 days after last dose of study treatment.
* In Spain, Chile, and Argentina: Only cohorts G and H will be open to enrollment.

Key

Exclusion Criteria

Exclusion Criteria:

* Radiotherapy ≤ 14 days prior to first dose of study drug (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study treatment).
* Treated with systemic anti-cancer therapy or an investigational agent within 2 weeks prior to start of study drug treatment (within 4 weeks for immunotherapy and tyrosine kinase inhibitor therapy).
* Subjects who experienced Grade 3 or higher immune-related toxicity from prior immuno-oncology therapy.
* Major surgery ≤ 30 days prior to first dose of study drug, or has not recovered to at least Grade 1 from adverse effects from such procedure, or anticipation of the need for major surgery during study treatment.
* Active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
* Primary central nervous system (CNS) disease or leptomeningeal disease; known CNS metastases unless treated, are asymptomatic, are without evidence of radiological progression for at least 8 weeks, and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days prior to Screening.
* Abnormal pulmonary function within the previous 6 months, including pneumonitis, active pneumonitis, interstitial lung disease requiring the use of steroids, idiopathic pulmonary fibrosis, confirmed pleural effusion, severe dyspnea at rest or requiring supplementary oxygen therapy.
* Parenteral antibiotics within 14 days of the first dose of study drug.
* History of allogenic or solid organ transplant.
* Uncontrolled diabetes mellitus or other uncontrolled immune-related endocrinopathies in the opinion of the Investigator.
* Known human immunodeficiency virus (HIV) infection or active infection with hepatitis C.
* For known uncontrolled hepatitis B virus (HBV) infection:

i. Anti-HBV therapy started before initiation of IMP and HBV viral load