A Phase 1 of CTX-8371 in Patients With Advanced Malignancies

Inclusion Criteria:

1. Age 18 years or older

2. Patients must have a histologically or cytologically confirmed diagnosis of locallyadvanced unresectable or metastatic disease that is relapsed/refractory to standardtherapy or for which no effective standard therapy is available, including

3. Malignant Melanoma (MM)

• Patients who have progressed after a minimum of 2 doses of a PD-1/PD-L1treatment. Study enrollment (C1D1) must be within 12 weeks of the lastdose of the anti-PD-1/PD-L1 blocking antibody.
• Patients must have had prior testing for BRAF V600 mutations.- Patientswith BRAF V600 activating mutation must have received prior therapy with aBRAF/MEK inhibitor.
• Uveal and mucosal melanoma are excluded.

2. Head and Neck squamous cell carcinoma (HNSCC)

• HNSCC of oral cavity, oropharynx, hypopharynx, or larynx
• Patients who have progressed after a minimum of 2 doses of a PD-1/PD-L1treatment. Study enrollment (C1D1) must be within 12 weeks of the lastdose of the anti-PD-1/PD-L1 blocking antibody.
• Patients must have received prior treatment with platinum-basedchemotherapy.

3. Non-Small Cell Lung Cancer (NSCLC)

• Patients who have progressed after a minimum of 2 doses of a PD-1/PD-L1treatment. Study enrollment (C1D1) must be within 12 weeks of the lastdose of the anti-PD-1/PD-L1 blocking antibody.
• Patients must have received prior treatment with platinum-basedchemotherapy.

4. Triple Negative Breast Cancer (TNBC)

• ER/PR and HER2 status should be defined by ASCO/CAP guidelines (JCOAllison et al 2020).
• Patients with HER2-low cancers (IHC 1+ or FISH-negative) are excluded.
• Patients must have received prior sacituzumab govitecan and if PD-L1 ≥10%by CPS pembrolizumab with chemotherapy.

5. Classical Hodgkin Lymphoma (HL)

• Patients must have received at least two prior systemic therapiesincluding brentuximab vedotin (if eligible) and a prior PD-1 inhibitor
• Patients must have experienced less than a CR (according to Luganocriteria to anti- PD-1 treatment

3. Patients with NSCLC, MM, TNBC, and HNSCC must have measurable disease per RECIST 1.1. Patients with HL must have at least one measurable lesion > 1.5 cm for nodal, > 1.0 cm for extranodal FDG-avid disease by the Lugano (2014) response criteria. Tumorsites that are considered measurable must not have received prior radiation

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

5. Adequate bone marrow function defined by absolute neutrophil (ANC) of ≥ 1.5×109/L,platelet count of ≥ 100.0×109/L, and hemoglobin of ≥ 9.0 g/dL (with or withouttransfusion)

6. Adequate hepatic function defined as serum total bilirubin ≤ 1.5 × ULN, AST/ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases)

7. Adequate renal function defined as creatinine clearance ≥ 30mL/min byCockcroft-Gault equation

8. Female patients must be surgically sterile (or have a monogamous partner who issurgically sterile) or be at least 2 years postmenopausal or commits to use 2acceptable forms of birth control (defined as the use of an intrauterine device (IUD), a barrier method with spermicide, condoms, any form of hormonalcontraceptives) or abstinence for the duration of the study and for 4 monthsfollowing the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birthcontrol (condoms with spermicide) for the duration of the study and for 4 monthsfollowing the last dose of study treatment.

9. Female patients who are women of childbearing potential (WOCBP) must have a negativeserum pregnancy test at Screening within 7 days of dosing with CTX-8371

10. Last dose of previous PD-1 or PD-L1 therapy ≥ 28 days, other anticancer therapy > 21days (or 2 half-lives for proteins, whichever is longer), radiotherapy >21 days (concurrent localized palliative radiotherapy is allowed during CTX-8371 treatment),or surgical intervention >21 days prior to the first dose of CTX-8371

11. Resolution of all prior anti-cancer therapy toxicities ≤ Grade 2

12. Capable of understanding and complying with protocol requirements

13. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any protocol-directed screeningprocedures are performed

Exclusion Criteria:

1. Developed clinically significant adverse reaction to PD-1 or PD-L1 therapy,including immune related adverse reactions, which led to discontinuation oftreatment

2. Systemic therapy with immunosuppressive agents within 7 days before the start ofCTX-8371 treatment. Topical, intranasal, intraocular, or inhaled corticosteroids andphysiologic replacement for patients with adrenal insufficiency are allowed

3. Patient is a pregnant or lactating WOCBP

4. Prior organ transplantation

5. Patients with evidence of active hepatitis B virus (HBV), hepatitis C virus (HCV) orhuman immunodeficiency virus (HIV) infection. Patients with positive HBsAg and/ordetectable HBV DNA are eligible only if adequately controlled on antiviral therapyaccording to institutional standards and liver function eligibility criteria arealso met. HCV patients showing sustained viral response or patients with immunity toHBV infection may enroll.

6. Active autoimmune disease or medical conditions requiring chronic steroid (i.e., > 10 mg/day prednisone or equivalent) or immunosuppressive therapy. Patients with aprior history of autoimmune disease may be eligible following discussion with theMedical Monitor

7. Other medical condition that in the opinion of the Investigator and/or SponsorMedical Monitor may interfere with the conduct and/or interpretation of the currentstudy, including:

8. Congestive heart failure (> New York Heart Association Class II), activecoronary artery disease, unevaluated new onset angina within 3 months orunstable angina (angina symptoms at rest) or clinically significant cardiacarrhythmias

9. QTc interval (using Fridericia correction calculation) > 480 msec