CBX-663 for Recurrent or Progressive Glioblastoma

Inclusion Criteria: Cohort A (R/R AML, MDS or CMML) Specific Inclusion Criteria: 1. R/R AML, as defined by standardized criteria (e.g., European Leukemia Net criteria (Dohner, 2022) (Arber, 2022); after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible. Participants must have bone marrow blasts ≥5%. 2. R/R MDS as per WHO 2022. Participants must have peripheral or bone marrow blasts \<20%, and must have exhausted locally available treatments, including treatments for actionable mutations. a. For High-Risk MDS participants, participants must be resistant to or refractory to at least 4 cycles of hypomethylating agents or have progressed or are intolerant to such agents. 3. R/R dysplastic or proliferative CMML participants, participants must be resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine). 4. White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment. 5. Any prior treatment-related toxicities resolved to Grade ≤1 prior to enrollment, with the exception of Grade ≤2 alopecia. Cohort B (Solid Tumor) Specific Inclusion Criteria: 6. Histologically or cytologically diagnosed, locally advanced (unresectable) or metastatic solid cancers that have progressed after all available standard therapy for the specific tumor type, or for which no standard therapy exists. Participants for whom standard therapies are intolerable or considered inappropriate by the Investigator are eligible. 7. Measurable disease (as defined by RECIST version 1.1). Prior Therapy 8. Any prior treatment-related toxicities resolved to Grade ≤1 prior to enrollment, with the exception of Grade ≤2 alopecia. 9. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician. 10. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors. 11. Anti-Cancer Therapy: Chemotherapy or small molecule targeted therapy, either investigational or commercially approved and available, within 2 weeks or 5 half-lives (whichever is shorter) prior to the start of study drug administration. 12. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port). Cohort C (Recurrent/Progressive GBM) Specific Inclusion Criteria: 13. Histologically confirmed or molecularly defined diagnosis of glioblastoma (IDH-wildtype) according to WHO 2021. 14. Historical documented evidence of a TERT promoter mutation. 15. Radiographic evidence of recurrent or progressive disease following prior first-line radiotherapy, defined as progression per RANO 2.0 criteria, as determined by investigator assessment. Prior use of tumor-treating fields is allowed but not required (Wen, 2023). 16. Measurable (at least 1 cm x 1 cm) enhancing tumor. 17. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia and ≤Grade 2 fatigue. Inclusion Criteria for All Participants: 18. Aged ≥18 years. 19. Backfill Cohorts: Participants for whom no curative treatment options, including transplantation, are available. 20. Historical documented evidence of HLA-A\*02:01 allele positivity. 21. ECOG PS score 0-1. Adequate Organ Function Requirements within 10 Days of Treatment Initiation 22. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 based on local institutional practice (e.g., Cockcroft-Gault formula). 23. Adequate liver function defined as: * Total bilirubin \<1.5 × the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 × ULN (unless attributed to leukemic or tumor involvement with discussion with the Study Responsible Physician). 24. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose. 25. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose. 26. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions. Exclusion Criteria: Cohort C (Recurrent/Progressive GBM) Specific Exclusion Criteria: 1. Known or suspected leptomeningeal disease are excluded, defined as radiographic evidence of leptomeningeal involvement on MRI of the brain and/or spine, or positive cerebrospinal fluid (CSF) cytology, at screening or prior to first dose. 2. Tumors involving the brainstem or spinal cord are excluded, including primary tumors arising from, or metastatic lesions involving, the brainstem (midbrain, pons, or medulla) or spinal cord. 3. Received prior bevacizumab or any other anti-VEGF or anti-VEGFR therapy. 4. Absolute lymphocyte count \<800/uL. 5. Clinically significant mass effect or midline shift. Exclusion Criteria for All Participants: 6. Previous treatment with any pHLA-targeting T-cell engager. 7. Isolated extramedullary relapse. 8. Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy. • Note: this does not apply to Cohort C GBM participants 9. Known HIV infection. 10. Active hepatitis B infection (participants with documented clearance following treatment are allowed). 11. Active hepatitis C infection (participants with documented clearance following treatment are allowed). 12. Any acute or chronic infection requiring systemic treatment 13. Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 14. Cardiac Disease: * Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class \>II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. * QTc using Fridericia's correction (QTcF) \>480 msec 15. Graft-Versus-Host Disease (GVHD): Active GVHD. 16. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe. 17. Current or historical diagnosis of a gastrointestinal autoimmune or inflammatory condition, including but not limited to ulcerative colitis (UC), Crohn's disease (CD), indeterminate colitis, or microscopic colitis (collagenous or lymphocytic colitis), or a history of GI toxicity from previous therapy that, in the opinion of the investigator, should preclude study participation. 18. Significant impairment of lung function requiring chronic use of ambulatory supplemental oxygen. 19. Screening laboratory values or investigations that do not meet the requirements for adequate organ function. 20. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate. 21. Any commercially available or investigational anti-leukemic or anti-cancer therapy other than CBX 663, with the following exceptions: • Intrathecal chemotherapy for CNS prophylaxis is permitted after C1 is complete, at the treating physician's discretion. 22. Participants who experienced severe, life-threatening or recurrent (≥ Grade 2) immune-mediated adverse events or infusion-related reactions including those that led to permanent discontinuation while on previous treatment with immuno-oncology agents. 23. Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted. Participants who stopped calcineurin inhibitor (CNI) prophylaxis should be off CNI for at least 4 weeks. 24. Known allergy or sensitivity to study drug, including excipients.