This is a phase II single arm efficacy/safety trial that will evaluate the effectiveness of
combining intensive locoregional intraperitoneal (IP) chemoimmunotherapy of cisplatin with IP
rintatolimod (TLR-3 agonist) and IV infusion of the checkpoint inhibitor pembrolizumab (IVP)
for patients with recurrent platinum-sensitive ovarian cancer (OC).
Patients will receive a total of six treatment cycles, at 3-week intervals. The study will
use an IP neoadjuvant approach (IP chemoimmunotherapy of cisplatin with IP rintatolimod and
IV infusion of pembrolizumab), followed by interval cytoreduction (usually laparoscopically)
of residual tumor. Cytoreduction will occur approximately 4 weeks after the fourth treatment
cycle. Post-surgery the investigators will consolidate with 2 additional courses of same
chemo-immunotherapy regimen. Catheter will be removed 12 weeks after the last treatment. All
surgical procedures, if done laparoscopically, are outpatient and will yield up to three
serial biopsies of the tumor sites: 1) at catheter placement; 2) at interval cytoreduction
which consists of removal of any visible tumor sites and the site biopsied initially whether
tumor is present or not; 3) at catheter removal, when site of first tumor biopsy will be
re-biopsied for pathologic response.
1. Patients must be at least 18 years of age on the day of signing informed consent.
2. Patients must have first or second peritoneal recurrence of epithelial adenocarcinoma
or carcinosarcoma of ovarian, tubal or peritoneal origin:
1. Histologic documentation of the original primary tumor is required via the
2. Original tumor blocks from the primary diagnosis will be requested by our study
pathologist at Magee-Womens Hospital of UPMC Cancer Centers. Original tumor
blocks may be reviewed after registration (informed consent and enrollment).
3. Patients must have completed prior platinum-based therapy. Response can be complete or
partial if it otherwise meets platinum sensitive criteria, see below.
4. Patients must be platinum-sensitive, defined as having a progression free interval
(PFI) of more than 6 months (180 days) from any platinum therapy. Patients are allowed
to have had other lines of therapy since last platinum if PFI after platinum therapy
meets platinum sensitive criteria.
5. Patients must have measurable disease in the peritoneal cavity, measurable per RECIST
1. A mass with a length of 1.0 cm or greater and/or
2. A lymph node with a length of 1.5 cm or greater in the shortest axis.
6. Patients must be a reasonable candidate for laparoscopy and IP platinum regimen with
no prior evidence of clinically significant intra-abdominal adhesions, persistent
abdominal wall infections, renal toxicity or bowel obstruction.
7. Patients of childbearing potential must:
1. Have a negative pregnancy test prior to the study entry.
2. Must discontinue breastfeeding prior to the first date of treatment on this study
3. Agree to follow the contraceptive guidance in Appendix 3 during the treatment
period and for at least 120 days after the last dose of study treatment.
8. Patients must agree to the protocol designated clinical monitoring to receive the
9. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the date of
11. Have adequate organ function as defined in the following table (Table 1). Specimens
must be collected within 14 days prior to the start of study treatment.
1. A woman of child-bearing potential who has a positive urine pregnancy test within 72
hours prior to infusion of treatment regimen (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
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 (e.g.,
CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to allocation.
- Note: Participants must have recovered from all AEs due to previous therapies to
≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
- Note: If participant received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
4. 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.
5. Patients who received maintenance therapy after the prior platinum therapy. An
exception to this exclusion would be if the PFI is greater than 6 months (180 days)
off of the maintenance agent or a PFI greater than a 1 year (365 days) regardless of
the duration of maintenance therapy.
6. Patients with previous pelvic radiation therapy.
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 (e.g., 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
o 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
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.
10. Patients with tumors of low malignant potential, except ovarian pseudomyxomas, or with
no peritoneal disease.
11. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.
o 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.
12. Has known active CNS metastases and/or carcinomatous 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.
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
14. Has a known allergy to cisplatin chemotherapy. Patients with carboplatin allergy may
be included if they tolerate a test dose of IV cisplatin given in monitored floor
15. 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.
16. Has a history of (non-infectious) pneumonitis that required steroids or has current
17. Has an active infection requiring systemic therapy.
18. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is
required unless mandated by local health authority.
19. 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.
20. Has a known history of active TB (Bacillus Tuberculosis)
21. 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.
22. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
23. Is pregnant or breastfeeding, or expecting to conceive or within the projected
duration of the study, starting with the screening visit through 120 days after the
last dose of trial treatment.