Summary

This is a Phase 1, open-label, first-in-human study of CTX-8371 administered as a
monotherapy in patients with metastatic or locally advanced malignancies. The study will
be conducted in 2 cohorts: Dose Escalation and Dose Expansion.

Objectives

This Phase 1, open-label, first-in-human study will evaluate the safety, tolerability,
immunogenicity, and pharmacokinetic profile of CTX-8371 monotherapy. Preliminary
anti-tumor activity of CTX-8371 will also be assessed. The study will be conducted in 2
cohorts: Dose escalation and Dose expansion. The Dose Escalation Cohort will utilize a
3+3 design to evaluate five dose levels (0.1-10.0 mg/kg) of CTX-8371 given as an IV
infusion once every 2 weeks. Patients in the Dose Expansion Cohort will receive CTX-8371
as an IV infusion at 3.0 mg/kg or 10.0 mg/kg at a 1:1 allocation.

Eligibility

1. Age 18 years or older
2. Patients must have a histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic disease that is relapsed/refractory to standard therapy or for which no effective standard therapy is available, including
3. Malignant Melanoma (MM)
4. Patients who have progressed after a minimum of 2 doses of a PD-1/PD-L1 treatment. Study enrollment (C1D1) must be within 12 weeks of the last dose of the anti-PD-1/PD-L1 blocking antibody
5. Patients must have had prior testing for BRAF V600 mutations. Patients with BRAF V600 activating mutation must have received prior therapy with a BRAF/MEK inhibitor
6. Uveal and mucosal melanoma are excluded
7. Head and Neck squamous cell carcinoma (HNSCC)
8. HNSCC of oral cavity, oropharynx, hypopharynx, or larynx
9. Patients who have progressed after a minimum of 2 doses of a PD-1/PD-L1 treatment. Study enrollment (C1D1) must be within 12 weeks of the last dose of the anti-PD-1/PD-L1 blocking antibody
10. Patients must have received prior treatment with platinum-based chemotherapy
11. Non-Small Cell Lung Cancer (NSCLC)
12. Patients who have progressed after a minimum of 2 doses of a PD-1/PD-L1 treatment. Study enrollment (C1D1) must be within 12 weeks of the last dose of the anti-PD-1/PD-L1 blocking antibody
13. Patients must have received prior treatment with platinum-based chemotherapy
14. Triple Negative Breast Cancer (TNBC)
15. ER/PR and HER2 status should be defined by ASCO/CAP guidelines (JCO Allison et al 2020)
16. Patients with HER2-low cancers (HER2 IHC 1+ or 2+/ISH negative) are excluded
17. Patients must have received prior sacituzumab govitecan and if PD-L1 =10% by CPS pembrolizumab with chemotherapy
18. Classical Hodgkin Lymphoma (HL)
19. Patients must have received at least two prior systemic therapies including brentuximab vedotin (if eligible) and a prior PD-1 inhibitor
20. Patients must have experienced less than a CR (according to Lugano criteria) to anti- PD-1 treatment
21. (Cohort 2 Dose Expansion): Non-Small Cell Lung Cancer (NSCLC)
22. Patients who have progressed after a minimum of 2 doses of a PD-1/PD-L1 treatment
23. Patients must have received prior treatment with platinum-based chemotherapy
24. (Cohort 2 Dose Expansion) Triple Negative Breast Cancer (TNBC)
25. ER/PR and HER2 status should be defined by ASCO/CAP guidelines (JCO Allison et al 2020)
26. Patients must have received prior sacituzumab govitecan and if PD-L1 =10% by CPS pembrolizumab with chemotherapy
27. Patients with HER2-low tumors need to have received fam-trastuzumab deruxtecan (Enhertu)
28. 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. Tumor sites that are considered measurable must not have received prior radiation
29. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
30. 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 without transfusion) a. (Cohort 2 Dose Expansion) 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 without transfusion) within 2 weeks from the first dose of CTX-8371.
31. Blood transfusion is not allowed within 2 weeks from the first dose of CTX-8371
32. Adequate hepatic function defined as serum total bilirubin = 1.5 × ULN, AST/ALT = 2.5 × ULN (or = 5 × ULN in patients with liver metastases)
33. Adequate renal function defined as creatinine clearance = 30mL/min by Cockcroft-Gault equation
34. Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be at least 2 years postmenopausal or commits to use 2 acceptable forms of birth control (defined as the use of an intrauterine device (IUD), a barrier method with spermicide, condoms, any form of hormonal contraceptives) or abstinence for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment
35. Female patients who are women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening within 7 days of dosing with CTX-8371
36. Last dose of previous PD-1 or PD-L1 therapy = 28 days, other anticancer therapy > 21 days (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
37. Resolution of all prior anti-cancer therapy toxicities = Grade 2
38. Life expectancy = 12 weeks
39. Capable of understanding and complying with protocol requirements
40. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any protocol-directed screening procedures are performed

Treatment Sites in Georgia