A non randomized, unblinded, open label phase 2 study to investigate the efficacy of
pembrolizumab in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) with
PD-L1 genetic alterations
1. Male/female participants who are at least 18 years of age on the day of signing
informed consent with a histologically confirmed diagnosis of DLBCL will be enrolled
in this study.
Note: Patients with high-grade B cell lymphomas not otherwised specified and those
with MYC and BCL2 translocations (double hit lymphoma) are eligible, as are patients
with transformed indolent lymphoma, so long as PD-L1 gene alterations are present.
2. A male participant must agree to use a contraception during the treatment period and
for at least 120 days after the last dose of study treatment. Participants must
refrain from donating sperm during this period.
3. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP)
2. A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 120 days after the last dose of study treatment.
C.) patient must have negative pregnancy test within 72 hours of beginning treatment
4. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
5. Have measurable disease, defined as at least one lesion that can be accurately
measured in at least two dimensions by CT scan. Minimum measurement must be >15 mm in
the longest diameter by >10 mm in the short axis. Lesions situated in a previously
irradiated area are considered measurable if radiographic progression has been
demonstrated in such lesions.
6. Participants must have available archived biopsy material (ideally to be performed
shortly before enrollment at the time of most recent relapse) for PD-L1 FISH and
7. There is evidence of a PD-L1 gene alteration within lymphoma cells as assessed by
8. Participants must have received ≥ 2 lines of prior systemic therapy, ≥ 1 line of prior
systemic therapy (if ineligible for or refused autologous stem cell transplantation),
or have received 1 line of prior therapy with primary-refractory disease or have
relapsed within 12 months from the time of initial diagnosis.
Note: patients having undergone prior CAR T cell therapy are eligible, as are patients
having received a prior allogeneic transplantation, provided they do not meet any of
the exclusionary GVHD criteria, and are at least 5 years removed from the date of
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
10. Have adequate organ function within 10 days prior to the date of treatment allocation.
Please see below for Adequate Organ Function Laboratory Values:
- Absolute neutrophil count (ANC) less than or equal to 1,000/microliters
- Platelets less than or equal to 50,000/microliters
- Hemoglobin less than or equal to 8.0 grams per decilitre
- Creatinine OR measured or calculated clearance (GFR can also be used in
place of creatinine or CrCl) greater than or equal to 1.5XULN OR less than
or equal to 30mL/min for participant with creatinine levels less than 1.5 X
- Total bilirubin greater than or equal to 1.5 X ULN or direct bilirubin
greater than or equal to ULN for participants with total bilirubin levels
less than 1.5 x ULN
- AST (SGOT) and ALT (SGPT) greater than or equal to 2.5 x ULN (greater than
or equal to 5 x ULN for participants with liver metastases)
- International normalized ratio (INR) OR prothrombin time (PT) and Activated
partial thromboplastin time (aPTT) greater than or equal to 1.5 x ULN unless
participant is receiving anticoagulant therapy as long as PT or aPTT is
within therapeutic range of intended use of anticoagulants.
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment
allocation . If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
3. Has received chemotherapy, monoclonal antibody therapy, or targeted small molecule
therapy within 4 weeks prior to the first dose of study medication. Subjects must have
recovered (≤ Grade 1) from adverse events related to a previously administered agent
(patients with ≤ Grade 2 neuropathy are eligible). Subjects who have previously
received CAR T cell therapy are eligible provided that relapse occurred > 90 days
following the date of CAR T cell infusion.
Note: If a participant received major surgery, he or she must have recovered
adequately from complications from the intervention prior to starting study treatment.
4. Has received prior radiotherapy within 1 week of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis.
5. Has a histologic diagnosis of primary mediastinal lymphoma or gray zone lymphoma.
6. Has known active CNS lymphoma and/or lymphomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment.
7. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
8. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug. Short
courses of corticosteroids will be allowed for palliation of symptoms related to
lymphoma, but must be discontinued within 7 days prior to the first dose of study
10. Subjects having received prior allogeneic stem cell transplant, must be at least 5
years removed from the date of their transplant. The also must have no history of
severe (grade 3-4) acute GVHD, and/or current > grade 1 acute GHVD. Subjects must not
have active chronic GVHD that requires active immune suppression or more than 10 mg of
prednisone/day or equivalent.
11. Has a history of a solid organ transplant.
12. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that
have undergone potentially curative therapy are not excluded
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
14. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
15. Has a history of (non-infectious) pneumonitis that required steroids or has current
16. Has an active infection requiring systemic therapy.
17. Has a known history of Human Immunodeficiency Virus (HIV) infection.
18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as detection of HCV RNA)
19. Has a known history of active TB (Bacillus Tuberculosis).
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
21. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
22. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.