A Dose Escalation Study of Duvortuxizumab in Participants With Relapsed or Refractory B-cell Malignancies

This first in human study consists of 2 parts: a) The dose escalation part and b) The dose
expansion part. This is an openlabel (all participants know the identity of the
intervention), multicenter (more than one study site) study to evaluate the safety, establish
a recommended Phase 2 dose (RP2D), and to determine the preliminary efficacy of
duvortuxizumab in participants with relapsed or refractory B cell malignancies. The dose
escalation part of the trial (Part 1) will be comprised of 3 different patient groups based
on disease indication: Group 1 (DLBCL, FL, MCL); Group 2 (CLL); Group 3 (ALL). The
duvortuxizumab dosing will be done on biweekly and weekly basis. Duvortuxizumab weekly
escalating dosing will be investigated. Dose escalation will begin with Group 1 and will
initially follow an accelerated dose titration design, followed by a traditional 3+3 design.
At each dose escalation level the treatment of the second participant should be initiated
after at least 72 hours of observation after the start of the first duvortuxizumab dose of
the first participant. Dose escalation in Groups 2 and 3 will follow a 3+3 design and will
begin after the initial dose level in Group 1 is deemed safe. Participants [Group 1 (DLBCL,
FL, MCL), Group 2 (CLL) Group 3 (ALL)] are enrolled into cohorts of increasing dose levels of
duvortuxizumab administered in 28 day treatment cycles. Up to 3 RP2Ds may be determined in
Part 1 (one RP2D for Group 1, one RP2D for Group 2, and one RP2D for Group 3). In the cohort
expansion part of the trial (Part 2), participants with relapsed or refractory B cell
malignancies (DLBCL, FL, MCL, CLL and ALL) will be enrolled according to tumor type in up to
5 cohorts and receive duvortuxizumab at the RP2D determined in Part 1 for their disease type.
The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of
study drug); Treatment period [first dose of study drug until the End of Treatment Visit
(within 30 days after the last dose)]; and follow up period [End of Treatment Visit and
continue until death, lost to follow up, consent withdrawal, or study end (as determined by
the sponsor), whichever occurs first]. Number of participants who achieve an overall response
in each Dose Expansion cohort will be evaluated primarily. Participants' safety will be
monitored throughout the study.

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Participants must meet protocol specified hematology and chemistry lab parameters
criteria

- Histological confirmation of disease with documented disease relapse after the last
therapy requiring treatment per the treating physician. Participants with lymphoma
must have at least 1 measurable site of disease (Part 2 only). In addition, B-cell
malignancy disease-specific criteria specified in the protocol must also be met

- A woman of childbearing potential must have a negative highly sensitive serum
[beta-human chorionic gonadotropin (β-hCG)] or urine pregnancy test at (minimum
sensitivity 25 International units (IU)/ liter (L) or equivalent units of HCG) within
7 days prior to the first dose of study drug

- A woman must agree to use an effective method of birth control and agree not to donate
eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for
3 months after receiving the last dose of study drug

- A man who is sexually active with a woman of childbearing potential must agree to use
a barrier method of contraception (eg, condom with spermicidal
foam/gel/film/cream/suppository), man who is sexually active with a woman who is
pregnant must use a condom and men must agree not to donate sperm for 90 days after
the last dose of study drug

- Each participant (or their legally acceptable representative) must sign an informed
consent form (ICF) indicating that he or she understands the purpose of and procedures
required for the study and are willing to participate in the study. Consent is to be
obtained prior to the initiation of any study related tests or procedures that are not
part of standard of care for the participant's disease

Exclusion Criteria:

- History of, or known central nervous system (CNS) involvement caused by the underlying
B-cell malignancy or prior history of National Cancer Institute common terminology
criteria for adverse events (NCI CTCAE) Grade greater than or equal to >= 3
drug-related CNS toxicity. Participants with signs or symptoms of CNS involvement
should have a computed tomography (CT) or magnetic resonance imaging (MRI)

- History of or known or suspected autoimmune disease (exception: vitiligo, resolved
childhood atopic dermatitis, and history of Grave's disease that is euthyroid
clinically and by laboratory testing at Screening)

- Prior allogeneic hematopoietic stem-cell transplant for participants with DLBCL, FL,
MCL, and CLL only. Prior allogenic hematopoietic stem-cell transplant is permitted for
participants with ALL

- Prior solid organ transplantation

- Prior treatment with a therapeutic agent targeting CD19 and/or CD3