PHASE 1/2 MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ONCT-808 IN ADULT SUBJECTS WITH RELAPSED OR REFRACTORY AGGRESSIVE B-CELL MALIGNANCIES

This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy,
ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies.

Key Inclusion Criteria:

- Over 18 years old

- Histologically confirmed aggressive B-cell NHL, including:

- MCL, with diagnosis confirmed by cyclin D1 overexpression or evidence of t
(11;14) translocation

- LBCL, including:

- DLBCL NOS

- Primary mediastinal LBCL

- High-grade BCL

- DLBCL arising from follicular lymphoma

- Follicular lymphoma grade 3B

- Richter's syndrome

- Availability of archival tissue for immunohistology, or willing to undergo baseline
biopsy if not available

- R/R with no available therapy. Subject must have:

- Received prior systemic therapy that has included an alkylating agent,
anthracycline, and an anti-CD20 mAb

- Received and progressed after autologous hematopoietic stem cell transplant
(HSCT) or is ineligible for or has refused to receive HSCT

- Received prior approved CD19 CAR T-cell therapy or is ineligible for or has
refused CD19 CAR-T

- Minimum washout period between previous systemic therapy and leukapheresis includes:

- Chemotherapy: at least 14 days or 5 half-lives, whichever is shorter

- Autologous HSCT: at least 3 months

- CD19 CAR T-cell therapy: at least 6 months

- ≥1 measurable lesion per Lugano criteria (Cheson, 2014)

- Subject has Fluorodeoxyglucose (FDG)-avid disease.

- Subject has an ECOG performance status of 0 or 1.

- Subject has adequate organ function:

- ALC ≥100/uL

- ANC ≥1000/uL (≥500/uL if due to lymphoma; growth factors allowed)

- Hgb ≥8 g/dL (transfusion allowed)

- Platelets ≥75,000/uL (≥50,000/uL if due to lymphoma; transfusion allowed)

- CrCL ≥50 ml/min; AST/ALT ≤2.5x ULN, T. bili ≤1.5 mg/dl (except Gilbert's)

- EF ≥50% by ECHO/MUGA; NCS ECG, NCS pleural effusion; O2 sat >92%

- Subject has an estimated life expectancy of >12 weeks

Key Exclusion Criteria:

- Prior ROR1-targeted therapy

- Current or anticipated systemic immunosuppressive therapy (e.g., prednisone >5 mg)
from LD chemo until Day 28 post ONCT-808 dosing

- If receiving anticoagulation therapy, subject is unable to hold therapy for 3 days
prior and 28 days following ONCT-808 administration

- Known CNS involvement by malignancy within 6 months

- H/o or current CNS disorder (e.g., seizure, CVA, dementia, cerebellar disease,
cerebral edema, posterior reversible encephalopathy syndrome or any autoimmune disease
with CNS involvement) within 6 months of study entry

- Clinically significant cardiovascular disease (e.g., MI, UA, CABG, or CHF grade ≥2
NYHA within 12 months of planned ONCT-808 dosing) or serious arrhythmia requiring
medication

- Evidence of HIV infection or active HBV, HCV

- Systemic fungal infection requiring medication in the last 12 months

- H/o Covid-19 infection with residual lung infiltrate/fibrosis

- H/o other malignancy except non-melanoma skin cancer or carcinoma in situ not in
remission for ≥2 years

- H/o autoimmune disease resulting in end organ injury or require systemic
immunosuppression within last 2 years

- H/o allogeneic HSCT or organ transplant