A Safety and Efficacy Trial of JCAR017 Combinations in Subjects With Relapsed/Refractory B-cell Malignancies (PLATFORM)

This is a global, open-label, multi-arm, multi-cohort, multi-center, Phase 1/2 study to
determine the safety, tolerability, PK, efficacy and patient reported quality of life of
JCAR017 in combination with various agents. This protocol is intended to evaluate various
drug combinations with JCAR017, as separate arms, over the life of the protocol, using the
same objectives.

During the Phase 1 part, different arms may be opened to test JCAR017 in combination with
combination agent(s). Within each arm, different doses and schedules of JCAR017 and the
combination agent(s) may be tested in several cohorts and subcohorts per arm. During the
Phase 2 part of the study, the expansion of any dose level and schedule that has been shown
to be safe may occur.

Arm A will test JCAR017 in combination with durvalumab in adult subjects with R/R aggressive
B-cell NHL.

Arm B, will evaluate JCAR017 in combination with CC-122 in adult subjects with R/R aggressive
B-cell NHL.

All subjects from Phase 1 and Phase 2 will be followed for 24 months following JCAR017
infusion. Post-study follow-up for survival, relapse, long-term toxicity (including new
malignancies), and viral vector safety will continue under a separate long-term follow-up
(LTFU) protocol for up to 15 years after the JCAR017 dose as per health authority regulatory
guidelines.

Inclusion Criteria:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).

2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.

3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.

4. Subject must have histologically confirmed at last relapse aggressive B-cell NHL
according to "The 2016 revision of the WHO classification of lymphoid neoplasms"
defined as:

1. Diffuse large B-cell lymphoma (DLBCL) Not otherwise specified (NOS) including
transformed indolent Non-Hodgkin lymphoma (NHL)

2. Follicular lymphoma Grade 3B

3. T cell/histiocyte-rich large B-cell lymphoma

4. Epstein-Barr virus (EBV) positive DLBCL, NOS

5. Primary mediastinal (thymic) large B-cell lymphoma

6. High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with
DLBCL histology (double/triple-hit lymphoma)

5. Subjects disease must have relapsed or be refractory to at least 2 prior lines of
therapy. Previous therapy must have included a CD20-targeted agent and an
anthracycline.

6. Subject must have positron emission tomography (PET)-positive disease as per Lugano
Classification

7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 at screening

8. Adequate organ function

9. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for
usage in other individuals as detailed in the protocol

10. Participants must agree to use effective contraception

Exclusion Criteria:

1. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study based on
investigator´s judgment.

2. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study
based on investigator´s judgment.

3. Subject has any condition that confounds the ability to interpret data from the study
based on investigator´s judgment.

4. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the
subject has been free of the disease for ≥ 2 years with the exception of the following
non-invasive malignancies:

5. Basal cell carcinoma of the skin

6. Squamous cell carcinoma of the skin

7. Carcinoma in situ of the cervix

8. Carcinoma in situ of the breast

9. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor,
nodes, metastasis] clinical staging system) or prostate cancer that is curative.

10. Other completely resected stage 1 solid tumor with low risk for recurrence

11. Prior treatment with any prior gene therapy product

12. Prior treatment with any adoptive T cell therapy; prior hematopoietic stem cell
transplant (HSCT) is allowed

13. Allogeneic HSCT within 90 days of leukapheresis

14. Prior treatment with anti PD-1 or PD-L1 therapy (Arm A)

15. Prior use of CC-122 (Arm B)

16. Presence of acute or chronic graft-versus-host disease (GVHD)

17. History of or active hepatitis B or hepatitis C or human immunodeficiency virus (HIV)
infection

18. Uncontrolled bacterial, viral or fungal infection at the time of leukapheresis,
lymphodepleting chemotherapy or JCAR017 infusion

19. History of any one of the following cardiovascular conditions within the past 6
months: Class III or IV heart failure as defined by the New York Heart Association
(NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or
other clinically significant cardiac disease

20. History or presence of clinically relevant central nervous system (CNS) pathology such
as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia,
Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis

21. Subjects with active CNS or cerebrospinal fluid (CSF) involvement by malignancy

22. Pregnant or nursing (lactating) women.

23. Subjects with active auto immune disorders/processes or active neurological or
inflammatory disorders

24. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with
fludarabine or cladribine within 3 months of leukapheresis

25. Use of the following:

26. Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior
to JCAR017 administration. Physiologic replacement, topical, inhaled, and intranasal
steroids are permitted.

27. Low dose chemotherapy given after leukapheresis to maintain disease control must be
stopped ≥ 7 days prior to lymphodepleting chemotherapy.

28. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 week of
leukapheresis. Oral chemotherapeutic agents are allowed if at least 3 half-lives have
elapsed prior to leukapheresis.

29. Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine)
within 2 weeks of leukapheresis.

30. Experimental agents within 4 weeks of leukapheresis unless no response or disease
progression is documented on the experimental therapy and at least 3 half-lives have
elapsed prior to leukapheresis.

31. GVHD therapies within 4 weeks of leukapheresis and JCAR017 administration.

32. Donor lymphocyte infusions (DLI) within 6 weeks of JCAR017 administration

33. Radiation within 6 weeks of leukapheresis.

34. Live attenuated vaccines within 90 days prior to leukapheresis.