Overview

Bevacizumab and Pembrolizumab Combination in EBER-ISH Positive NPC

Status:
Not yet recruiting
Trial end date:
2024-03-01
Target enrollment:
0
Participant gender:
All
Summary
This is a single center, randomized, phase Ib/II open-label study of pembrolizumab (pembro or MK-3475) with or without bevacizumab in patients with recurrent non-curable or metastatic nasopharyngeal carcinoma (NPC).
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National University Hospital, Singapore
Collaborator:
Merck Sharp & Dohme Corp.
Treatments:
Bevacizumab
Pembrolizumab
Criteria
Inclusion Criteria:

- Participants are eligible to be included in the study only if all of the following
criteria apply:

1. The participant (or legally acceptable representative if applicable) provides written
consent for the trial.

2. Participants who are at least 21 years of age on the day of signing informed consent
with histologically or cytologically confirmed diagnosis of non-keratinizing
nasopharyngeal carcinoma (NPC) that has recurred at loco regional and/or distant sites
will be enrolled in this study.

3. Have measurable disease based on RECIST 1.1. Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
lesions.

4. Have locally or centrally determined EBV-positive NPC by EBV-encoded small RNA in situ
hybridization (EBER in situ hybridization [ISH]) assay. If EBV-positive status has
been previously determined by EBER ISH assay, then no re-testing is required. Note: If
EBV status by EBER ISH assay has not been previously determined, tumor tissue from
archival tissue may be submitted for EBV determination.

5. Received one or more lines of chemotherapy, which must include prior treatment with a
platinum agent and must not be amenable to potentially curative radiotherapy or
surgery.

6. Have provided archival tumor tissue sample of newly obtained core or excisional biopsy
of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
archived tissue. Note: If submitting unstained cut slides, newly cut slides should be
submitted to the testing laboratory within 14 days from the date slides are cut.

7. Willingness to donate blood and tissue for mandatory translational research studies.

8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

9. Have an adequate organ function.Specimens must be collected within 10 days prior to
the start of study treatment.

10. A female participant is eligible to participate if she is not pregnant (see Appendix
3), not breastfeeding, and at least one of the following conditions applies: a. Not a
woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who
agrees to follow the contraceptive guidance in Appendix 3 during the treatment period
and for at least 120 days after the last dose of study medication.

11. A male participant must agree to use a contraception as detailed in Appendix 3 of this
protocol during the treatment period and for at least 120 days after the last dose of
study treatment and refrain from donating sperm during this period.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to randomization. Note: Participants must have recovered from all
AEs to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2
neuropathy may be eligible. Note: If participants received major surgery, they must
have recovered adequately from the toxicity and/or complications from the intervention
prior to starting study treatment.

2. 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 first dose of
study treatment.

Note: Participants who have entered the follow-up phase of an investigational study
may participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.

3. Has a condition requiring systemic steroid therapy (> 10 mg daily prednisone
equivalents) or any other form of immunosuppressive therapy within 14 days prior to
the first dose of trial treatment. Inhaled or topical steroids and adrenal replacement
doses <10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease. Patients are permitted to use topical, ocular, intra-articular,
intranasal, and inhalational corticosteroids (with minimal systemic absorption).
Physiologic replacement doses of systemic corticosteroids are permitted, even if < or
= 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis
(e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g.,
delayedtype hypersensitivity reaction caused by contact allergen) is permitted.

4. Has a known history of active TB (Bacillus Tuberculosis).

5. Has had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, antiCTLA-4
antibody.

6. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.

7. Has hypersensitivity to bevacizumab or any of its components.

8. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.

9. 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, transitional cell carcinoma of urothelial cancer,
or carcinoma in situ (e.g. breast or cervical carcinoma in situ) that have undergone
potentially curative therapy are not excluded.

10. Has known brain metastases or leptomeningeal metastases, whether treated or untreated.
NOTE: Primary nasopharyngeal cancers that directly invade the skull base and extend
into the infratemporal fossa (e) are not regarded as brain metastases and are not
excluded.

11. 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 (e.g. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a
form of systemic treatment.

12. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.

13. Has an active infection requiring systemic therapy.

14. Has uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

15. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator

16. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

17. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.

18. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
randomization/allocation (see Appendix 3). If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required. Note: In the event
that 72 hours have elapsed between the screening pregnancy test and the first dose of
study treatment, another pregnancy test (urine or serum) must be performed and must be
negative in order for subject to start receiving study medication.

19. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is
required unless mandated by local health authority.

20. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Note: No testing for Hepatitis B and Hepatitis C is required
unless mandated by local health authority.

21. Has received a live vaccine within 30 days of 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-Guerin (BCG), and typhoid vaccine.

Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are
allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated
vaccines, and are not allowed.