Phase II Study to Evaluate Safety and Efficacy of CB-103 With Venetoclax in Adolescent and Young Adult Patients With Relapsed/Refractory T-ALL or T-LBL

Mixed phenotype leukemia (excluding T-ALL with myeloid antigen expression)

History of another primary invasive malignancy that has not been definitively treated and in remission. Participants with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).

Presence of clinically significant uncontrolled CNS pathology such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or psychosis.

Participants with a cardiac ejection fraction (as measured by either MUGA or echocardiogram) \< 50% or with a history of absolute decrease in LVEF of ≥ 15 absolute percentage points are excluded.

Medical history of cardiovascular disease such as

* Clinically significant cardiac disease including congestive heart failure (NYHA class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy

* Clinically uncontrolled hypertension Age Blood Pressure 12 to 13 = \>120/80mmHg \>13 = \>140/90mmHg

* Complete left bundle branch block

* Right bundle branch block + left anterior hemiblock

* Congenital long QT syndrome

* History or presence of sustained or symptomatic ventricular tachyarrhythmia, atrial fibrillation, or clinically significant resting bradycardia (\< 50 bpm)

* Corrected QT interval using Fridericia formula (QTcF) \> 450 ms for males and \> 470 ms for females at the screening ECG

* QRS ≥ 110 ms

* History of symptomatic congestive heart failure

Participants with uncontrolled, active infections (viral, bacterial, or fungal). Infections controlled on concurrent anti-microbial agents are acceptable. Anti-microbial prophylaxis per institutional guidelines is acceptable.

Known active hepatitis B or C infection or known seropositivity for HIV.

Liver cirrhosis or other active severe liver disease or suspected active alcohol abuse.

Have conditions requiring chronic systemic (not inhaled) glucocorticoid use, such as autoimmune disease or severe asthma. Low doses of corticosteroids (10 mg prednisone equivalent a day) are permitted.

Participants with unresolved nausea, vomiting, or diarrhea of CTCAE version 5.0, grade ˃

1 from prior therapy.

Participants with impairment of GI function or GI disease presence that may significantly alter the absorption of CB-103 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).

Have current or recurrent (within 3 months) gastrointestinal disease, have conditions requiring chronic systemic glucocorticoid use, have active graft versus host disease, or have a second primary or prior malignancy that would affect the interpretation of study results. Low doses of corticosteroids (10 mg prednisone equivalent a day) are permitted.

Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - Up to 5 days of glucocorticoids (10 mg of dexamethasone or equivalent/day) in combination with up to 3 doses of cyclophosphamide (200 mg/m2/day) are allowed as standard pre-phase treatment up to 1 day before start of study treatment.

Cytarabine up to 2gm/m2 are also allowed as standard pre-phase treatment up to 1 day before start of study treatment.

Mercaptopurine may be dosed up to 5 days prior to first dose of CB103

Vinca alkaloids may be dosed up to 5 days prior to first dose of CB103

Prophylactic intrathecal (IT) chemotherapy may be dosed up to 1 day prior to first dose of CB103

• Females who are pregnant or lactating

Male or female participants of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with institution's standards.

Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the Investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.

Participants who are unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures.

Participants must be excluded if they are currently enrolled in another ongoing clinical trial with anti-cancer investigational products

What this study is about