P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT03113487 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: 16448NCI-2017-00555P30CA033572
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well modified vaccinia virus ankara vaccine expressing p53 (p53MVA) and pembrolizumab work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving p53MVA and pembrolizumab together may work better in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

Conditions

Recurrent Platinum-Resistant Fallopian Tube Carcinoma; Recurrent Platinum-Resistant Ovarian Carcinoma; Recurrent Platinum-Resistant Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Patients Achieving Complete or Partial Response

  Clinical response was assessed using the modified irRECIST criteria. Complete Response (CR) - Disappearance of all lesions, 2 consecutive observations, ≥ 4 wks apart; Partial Response (PR) - ≥50% decrease in tumor burden from baseline, 2 consecutive observations, ≥ 4 wks apart. Response = CR+PR.

  Up to 24 months

Secondary Outcomes (3)

• Progression-free Survival

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 24 months

• Overall Survival

  From start of the treatment until death, assessed up to 24 months

• Clinical Benefit Rate

  Up to 24 months

Study Arms (1)

Treatment (pembrolizumab, p53MVA)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes every 3 weeks and modified vaccinia virus ankara vaccine expressing p53 SC every 3 weeks for up to 3 vaccines. Cycles with pembrolizumab repeat every 3 weeks for up to 49 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Modified Vaccinia Virus Ankara Vaccine Expressing p53; Biological: Pembrolizumab

Interventions

Modified Vaccinia Virus Ankara Vaccine Expressing p53 BIOLOGICAL

Given SC

Also known as: MVA-p53, MVA-p53 Vaccine, MVAp53 Vaccine, p53-MVA Vaccine, p53MVA

Treatment (pembrolizumab, p53MVA)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, p53MVA)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with histologically or cytologically confirmed diagnosis of epithelial ovarian, primary peritoneal or fallopian tube cancer will be enrolled in this study; patients must have experienced recurrence or progression within 6 months after completion of platinum based chemotherapy (by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria).
• A patient is eligible to participate if she is not pregnant, not breast-feeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Have measurable disease based on RECIST 1.1., or detectable disease; lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be greater than or equal to 10 mm when measured by computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI); lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT, PET/CT, or MRI
• Detectable disease in a patients is defined as one who does not have measurable disease, but has at least one of the following conditions:
• Baseline values of CA-125 at least 2 x upper limit of normal (ULN)
• Ascites and/ or pleural effusion attributed to tumor
• Solid and/ or cystic abnormalities on radiographic imaging that do not meet modified RECIST criteria, immune-related response criteria (irRC) for target lesions
• Patients whose ovarian cancer recurs/progresses within 0-6 months following platinum-based chemotherapy have platinum resistant or refractory disease; these patients are not considered to benefit from additional platinum-based therapy and are treated with other sequential single agents; such patients are eligible for this trial
• Patients with documented disease recurrence/progression within 6-12 months of completing platinum-based therapy, are considered to have 'borderline' platinum sensitivity; these patients will not be eligible for this trial
• Patients who relapse more than 12 months after completion of platinum-based treatment are considered 'platinum sensitive' and will not be eligible for this trial, since they have a favorable (33-59%) chance of responding to further rounds of platinum based chemotherapy
• Patients with confirmed p53 mutation by molecular analysis and/or evidence of p53 overexpression by immunohistochemistry (\>= 10% of cells within tumor staining positive) will be eligible; this will be assessed semi-quantitatively by a Clinical Laboratory Improvement Act (CLIA) approved pathology core pathologist, using CLIA approved mutational analysis or immuno-histochemistry techniques on formalin-fixed paraffin-embedded tissue; in the case of equivocal immunohistochemistry (IHC) results, p53 involvement may be confirmed by detection of p53 molecular analysis on tumor deoxyribonucleic acid (DNA); patients on whom molecular analysis of p53 mutations is already available, will not require IHC analysis; molecular analysis may be performed as an additional research procedure at the end of the study (distinct from eligibility determination) if the principal investigator (PI) deems it of scientific value and research funding is available to cover the cost; patients are not required to have PD-L1 positive ovarian tumors and PD-L1 testing is not mandatory on this study; however, we will collect the data on PD-L1 testing when available
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 (Karnofsky \>= 60%) and a life expectancy of at least 3 months
• Up to 4 prior chemotherapy regimens for recurrent disease are allowed; adjuvant chemotherapy and maintenance Taxol after completion of six cycles of adjuvant carboplatin - Taxol will not be counted as a "prior chemotherapy regimen" for the purpose of this study; treatment with targeted agents or hormones would not be considered as a systemic chemotherapy regimen; eligible Patients are those with documented disease recurrence/progression within 0-6 months of completing platinum-based chemotherapy; patients should not have received any non-oncology, viral vaccines within 30 days prior to starting protocol treatment

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to study treatment start; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• 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, OX-40, CD137)
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment start
• Note: participants must have recovered from all adverse events (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 study treatment
• Has received prior radiotherapy within 3 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-central nervous system (CNS) disease
• 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-Guerin (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
• 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 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
• Has a diagnosis of immunodeficiency (including organ grafts and human immunodeficiency virus \[HIV\]), or is receiving 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 (exceptions: nasal corticosteroids, inhaled steroids, adrenal replacement steroids and steroid creams are allowed)
• 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, superficial bladder cancer or any carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
• 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
• Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
• 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
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Interventions

MVAp53 vaccine; pembrolizumab

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Thanh Dellinger

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 13, 2017
• Study Start: February 1, 2018
• Primary Completion: August 26, 2022
• Study Completion: May 4, 2026
• Last Updated: July 20, 2025
• Results First Posted: October 8, 2024

Record last verified: 2025-07

Locations

US (1)