Olaparib, Durvalumab and UV1 in Relapsed Ovarian Cancer

NCT04742075 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ENGOT-OV56/NSGO-CTU-DOVACC
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, multicenter, open-label, randomized phase II maintenance study is evaluating the efficacy of UV1-olaparib-durvalumab combination as maintenance therapy after platinum combination therapy for BRCAwt patients with relapsed ovarian cancer.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is compared between arm A versus C

  72 months

Secondary Outcomes (5)

• PFS

  72 months

• PFS assessed by blinded independent central review (BICR)

  72 months

• Overall survival (OS)

  72 months

• Patient reported outcomes (PROs) - QLQ-OV28

  72 months

• Patient reported outcomes (PROs) - QLQ-C30

  72 months

Study Arms (3)

(A) Olaparib

ACTIVE COMPARATOR

Olaparib 300 mg tablets twice daily until progressive disease or unacceptable toxicity.

Drug: Olaparib + durvalumab + UV1

(B) Olaparib + durvalumab

EXPERIMENTAL

Olaparib 300 mg tablets twice daily until progressive disease or unacceptable toxicity. Durvalumab 1500 mg IV every 4 weeks for 24 months or until disease progression or unacceptable toxicity.

Drug: Olaparib + durvalumab + UV1

(C) Olaparib + durvalumab + UV1

EXPERIMENTAL

Olaparib 300 mg tablets twice daily until disease progression or unacceptable toxicity. Durvalumab 1500 mg IV every 4 weeks for 24 months or until disease progression or unacceptable toxicity. Eight UV1 vaccinations during the first 5 month: Four UV1 vaccinations 300 μg (+ 75 μg of sargramostim) during the first 10 days with a minimum of 2 days apart. From cycle 2-5 subjects will receive one UV1 (+ sargramostim) vaccination every 4th week.

Drug: Olaparib + durvalumab + UV1

Interventions

Olaparib + durvalumab + UV1 DRUG

The subjects are randomized 1:1:2 to receive treatment until progression of disease or untorable toxicity.

Also known as: Olaparib + durvalumab, Olaparib (active comparator)

(A) Olaparib; (B) Olaparib + durvalumab; (C) Olaparib + durvalumab + UV1

Eligibility Criteria

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

You may qualify if:

• Histologically diagnosed with epithelial ovarian, fallopian tube or primary peritoneal cancer, excluding mucinous or low-grade serous histology.
• Radiological or histological confirmation of relapse disease ≥ 6 months after penultimate chemotherapy.
• Patients who are non-gBRCAmut or tBRCAwt.
• Have completed at least two lines, but no more than 3 lines, of chemotherapy, which means that patients at first or second relapse with treatment free interval of more than 6 months on penultimate chemotherapy are eligible. See Figure 3.
• a. Patients must have completed at least 4 cycles of the latest platinum-containing chemotherapy.
• Be either:
• PARPi naive.
• Earlier treated with PARPi and not progressed during 6 months of PARPi therapy.
• Must not, in the opinion of the investigator, have progressed on, or after, latest platinumcontaining chemotherapy. This means that patients with CR, PR, SD or no evidence of disease are eligible. It should be documented on the post-treatment scan following completion of the last chemotherapy course.
• Patient consents to HRD test (Acceptable HRD tests: Myriad myChoice® CDx, Leuven HRD test, NOGGO GISv1, and TSO 500 HRD).
• Must be randomized in the study within 10 weeks of completion of the final dose of platinum-containing chemotherapy.
• Age ≥18 years.
• Body weight \> 30 kg.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix 3)
• Must have a life expectancy ≥ 16 weeks.

You may not qualify if:

• Previous use of immune checkpoint inhibitors.
• a. In case the patient has participated in an immune checkpoint inhibitor blinded study, the patient may be enrolled without unblinding.
• Other malignancy unless curatively treated with no evidence of disease for ≥ 5 years except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation ≥ 470 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study if these were started at least 4 weeks prior to treatment.
• Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan.
• Concomitant treatment with bevacizumab within the last 3 weeks.
• Concomitant therapy with any other anticancer therapy or chronic use of systemic corticosteroids of more than 10mg prednisolone daily.
• Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.
• Concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation.
• Major surgery or significant traumatic injury within 28 days of randomization.
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV), patients with active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C.

Sponsors & Collaborators

• Nordic Society of Gynaecological Oncology - Clinical Trials Unit: lead
• North Eastern German Society of Gynaecological Oncology: collaborator
• Belgian Gynaecological Oncology Group: collaborator
• Hellenic Cooperative Oncology Group (HeCOG): collaborator
• Arbeitsgemeinschaft Gynaekologische Onkologie Austria (AGO-Austria): collaborator
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator
• Dutch Gynaecological Oncology Group: collaborator

Study Sites (1)

Rigshospitalet

København Ø, Region Sjælland, 2100, Denmark

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib; durvalumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Design

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

Model Details: Open-label randomized phase 2 trial

Study Record Dates

• First Submitted: October 9, 2020
• First Posted: February 5, 2021
• Study Start: December 15, 2021
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

DK (1)