A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR0191 in Subjects with Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)

This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, dose-escalation, and
dose-optimization study to evaluate the safety and clinical activity of PBCAR0191 in adults
with r/r B ALL (Cohort A) and in adults with r/r B-cell NHL (Cohort N) and identify a
treatment regimen most likely to result in clinical efficacy while maintaining a favorable
safety profile.

Key Inclusion Criteria*

Criteria for B-ALL:

- Subject has unequivocal r/r CD19+ B-ALL that has been confirmed by morphology, flow
cytometry, or a validated minimal residual disease assay.

- Subjects with Philadelphia chromosome positive disease can be eligible if they are
intolerant to tyrosine kinase inhibitor therapy or if they have r/r disease.

Criteria for NHL:

- Subject has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by archived
tumor biopsy tissue from last relapse after CD19-directed therapy and corresponding
pathology report. Alternatively, if at least 1 tumor involved site is accessible at
time of Screening, the subject's diagnosis is confirmed by pretreatment biopsy
(excisional when possible) or by flow cytometry of fine needle aspirate. If a subject
never had a CR, a sample from the most recent biopsy is acceptable. NHL subtypes
included but are not limited to:

- Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation

- FL including Grade 3 or transformed FL

- High-grade B-cell lymphoma

- Primary mediastinal lymphoma

- Subject has measurable or detectable (for example positron emission
tomography-positive) disease according to the Lugano Classification.

- Subject must have received at least 2 prior chemotherapy-containing regimens,
consistent with standard of care treatment guidance (e.g., NCCN), unless no second
line therapy of known benefit exists for a given subject. Other than those
specifically prohibited, other therapies are allowed until 7 days prior to initiation
of LD. In that case, all Screening safety laboratories and disease assessments must be
performed after the last dose of prior therapy. For Richter's transformation, only 1
prior line of therapy is required for the DLBCL component.

- Subject has received no more than 7 systemic lines of anti-cancer therapy for the
disease under study.

- Subjects previously treated with CD19-directed autologous CAR T therapies have
received no more than 2 lines of therapy after administration of their previous CAR T
product.

- Expansion cohort only: Subjects must have received autologous CD19-directed CAR T
therapy and demonstrated clinical response to the treatment at Day 28 or later,
followed by relapse.

Criteria for both B-ALL and NHL:

- Eastern Cooperative Oncology Group performance status score of 0 or 1.

- An estimated life expectancy of at least 12 weeks according to the investigator's
judgment.

- Seronegative for human immunodeficiency virus antibody (i.e., intact immune function).

- Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
defined as:

1. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (calculated using
the CKD-EPI equation [Levey et al, 2009]). If there is a concern that eGFR
calculation is not an accurate reflection of renal function, a 24-hour urine
collection for creatinine clearance may be used at the investigator's discretion.

2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both
≤3 times of upper limit of normal (ULN), unless there is suspected disease in the
liver.

3. Total bilirubin <2.0 mg/dL, except in subjects with Gilbert's syndrome.

4. Platelet count ≥50,000/μL and absolute neutrophil count of ≥1000/ μL. Platelet
transfusions within 14 days of screening are not allowed except for subjects in
B-ALL disease cohort with extensive bone marrow disease burden, in which case
adequate bone marrow recovery after prior treatment is required to be documented.

5. C-reactive protein (CRP) <2x ULN; subjects with CRP elevation within 2x ULN,
ruling out infectious cause will be required.

6. Left ventricular ejection fraction >45% as assessed by echocardiogram (ECHO) or
multiple gated acquisition scan performed within 1 month before starting
lymphodepleting chemotherapy. ECHO results performed within 6 months before
Screening and at least 28 days after the last cancer treatment may be acceptable
if the subject has not received any treatment with cardiotoxicity risks.

7. No clinically significant evidence of pericardial effusion or pleural effusion
causing clinical symptoms and needing immediate intervention, based on the
investigator's opinion. Any known effusion must be stable without need for
drainage within 2 weeks of enrollment.

8. No clinically significant renal/pulmonary comorbidities.

9. Baseline oxygen saturation >92% on room air.

Key Exclusion Criteria*

Criteria for B-ALL:

- Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.

- No active central nervous system (CNS) disease. Subjects with a history of CNS
involvement must have a documented CR on at least 2 imaging studies at least 3 months
apart (with no masses in parenchyma and no ocular involvement) and a negative
cerebrospinal fluid cytology on at least 2 evaluations (one evaluation may be during
the Screening Period and the other must be at least 3 months prior).

Criteria for NHL:

- No prior or active CNS disease.

- Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or
blood vessel compression.

- Active hemolytic anemia.

Criteria for B-ALL and NHL:

- Subject has had a malignancy, besides the malignancies of inclusion (B-ALL or NHL),
that in the investigator's opinion, has a high risk of relapse in the next 2 years. In
the case of Richter's transformation, subjects may be enrolled with ongoing chronic
lymphocytic leukemia/small lymphocytic lymphoma.

- Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection that
has not resolved and does require therapeutic anti-microbial medications at least 7
days prior to LD. Subjects with elevated CRP must undergo infectious disease workup
and the recommendations discussed with medical monitor to be considered on an
individual basis. The CRP must be trending toward the normal range for the laboratory
with the exception when it's deemed related to the underlying malignancy.

- Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).

- Active hepatitis B or hepatitis C confirmed by PCR. Subject positive for inactive
hepatitis B is allowed to enroll if on prophylactic treatment.

1. Subject is seropositive for hepatitis B antigen with confirmation. If
confirmatory tests are negative, the subject can be enrolled.

2. Subject is seropositive for hepatitis C antibody unless antigen negative. If
hepatitis C antibody test is positive, the subject must be tested for the
presence of RNA by reverse transcription PCR and be hepatitis C virus-RNA
negative.

- Any known uncontrolled cardiovascular disease at the time of Screening that, in the
investigator's opinion, renders the subject ineligible, including but not limited to:

1. Active ventricular or atrial dysrhythmia ≥ Grade 2, bradycardia ≥ Grade 2.

2. Myocardial infarction within 6 months before Screening.

3. Pulmonary embolism, deep vein thrombosis, or any other significant coagulopathy
including disseminated intravascular coagulation.

- History of hypertension crisis or hypertensive encephalopathy within 3 months prior to
Screening. In case of hypertensive crisis caused by omission of well-established
treatment regimen, transient and promptly stabilized, enrollment must be discussed and
agreed upon with sponsor and medical monitor.

- History of severe immediate hypersensitivity reaction to any of the agents used in
this study.

- Presence of a CNS disorder that, in the opinion of the investigator, renders the
subject ineligible for treatment.

- Abnormal findings during the Screening Period or any other medical condition(s) or
laboratory findings that, in the opinion of the investigator, might jeopardize the
subject's safety.

- History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome,
Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.

- Active uncontrolled autoimmune disease requiring active immunosuppression at the time
of Screening (excluding subjects needing steroids for physiologic replacement).

- Subject has received stem cell transplant within 90 days before Screening.

- Subject has active GvHD symptoms.

- Subject has received systemic biologic agent for treatment of disease under study
within 28 days of LD or other systemic anti-cancer therapy within 10 days of LD Note:
this criterion does not apply if the subject has clear evidence of disease progression
after such an agent has been administered and all AEs have resolved to a Grade 2 or
less in severity. This should be discussed with the medical monitor for confirmation.

- Participation in noninterventional registries or epidemiological studies is not
excluded.

- Radiotherapy within 4 weeks before Screening should be discussed with monitor and
determined on a case-by-case basis.

- Presence of pleural/peritoneal/pericardial catheter, as well as biliary and ureteral
stents (does not apply to intravenous lines).

- Subject has received live vaccine within 4 weeks before Screening. Non-live virus
vaccines are not excluded.

- Subject has received CD19-directed therapy other than autologous CD19-directed CAR T
therapy within 90 days of the anticipated start date of LD.

- Additional criteria apply