Inclusion Criteria:

Histologically confirmed advanced solid tumors, such as but not limited to:

Lung squamous cell carcinoma (LSCC)
Esophageal squamous cell carcinoma (ESCC)
Head and neck squamous cell carcinoma (HNSCC)
Microsatellite stable colorectal cancer (MSS-CRC) that are refractory to standard therapy (to include standard chemotherapy and anti-PD-L1 therapy concurrently or sequentially prior to enrollment) or for which standard or curative therapy does not exist or is not considered appropriate by the Investigator. Patients with MSS-CRC must have completed at least 2 lines of standard of care treatments prior to enrollment.

Adequate hematologic (with no blood product or hematopoietic growth factor support during the prior 7 days), renal and hepatic function, as defined by the following laboratory values; test performed within 7 days prior to first dose of STI-6129:

a. Hematologic: i. Absolute neutrophil count (ANC) ≥ 1000 cells/μL ii. Platelet count ≥ 50,000 platelets/μL iii. Hemoglobin (Hgb) ≥ 8.0 g/dL b. Renal: creatine clearance (CrCl) ≥ 60 mL/min by Cockroft-Gault formula (Protocol Appendix 1) c. Hepatic: i. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ˂ 3x the upper limit of normal (ULN) ii. serum total bilirubin ˂ 1.5x ULN (except for patients in whom hyperbilirubinemia is attributed to Gilbert’s Syndrome) iii. Alkaline phosphatase times ˂ 3x ULN (˂ 5 times ULN if considered due to tumor)

ECOG performance status of 0 or 1
Be willing and able to comply with the study schedule and all other protocol requirements
Willing to follow contraception guidelines

Exclusion

Exclusion Criteria:

Use of systemic anti-tumor therapy or an investigational drug within 5 half-lives or 4 weeks of D1 whichever is shorter, preceding the first dose of study drug.
Received any prior anti-CD38 treatment within 90 days.
A diagnosis of other malignancies that have required systemic therapy within the last 3 years or is not in complete remission. Exceptions are non-metastatic basal cell or squamous cell carcinomas of the skin or prostate cancer or in situ cancer that does not require treatment or is well under control.
A current history of CTCAE Grade 3 muscle paresis, eyelid conditions, glaucoma controlled with medication or watering eyes or any other ocular disorder that is CTCAE Grade 2.
A history of a dose-limiting immune-related adverse event during PD-1 axis blockade.
INR or aPTT > 1.5 times ULN within one week prior to the infusion of STI-6129, unless on a stable dose of an anticoagulant
Patients with ≥ Grade 3 neuropathy or Grade 2 neuropathy with associated pain.
New York Heart Association (NYHA) Class > 2.
QTcF > 470 msec on a 12-lead ECG.
Treatment with potent inhibitors of cytochrome P450 systems: CYP3A4, CYP2B6 and CYP1A2, or strong inhibitors or transducers of transporter P-glycoprotein (Pgp or MDR1) or breast cancer resistance protein (BCRP or ABCG2) during the study. See https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers for details.
Symptomatic, untreated brain metastases. Patients with treated brain metastases may be treated at least 1 week after gamma knife stereotactic radiation or at least 2 weeks after whole brain radiation if symptoms have recovered with discontinuation of steroids. Patients with small, asymptomatic brain metastases may be considered for enrollment.
Symptomatic CNS disease (i.e. cord compression)