Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Rare Diseases

Recurrence

Carcinoma

Stomach Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Genital Neoplasms, Female

Urogenital Neoplasms

Neoplasms, Glandular and Epithelial

Ovarian Diseases

Endocrine Gland Neoplasms

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Endocrine System Diseases

Gonadal Disorders

Neoplasms by Histologic Type

Male Urogenital Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Ovarian Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Lenvatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.

200 mg administered by IV infusion on Day 1 of each 21-day cycle.

20 mg administered orally (PO) QD during each 21-day cycle.

Ronnie Shapira, MD

Ronnie Shappira, MD

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) for the treatment of platinum sensitive recurrent ovarian cancer. Participants will receive pembrolizumab and lenvatinib.

This will be a phase-2, open-label, single-arm, single-center study to assess the effect of pembrolizumab and Lenvatinib combination therapy on platinum-sensitive recurrent ovarian cancer (ROC) patients.

Female patients 18 years of age or older with histologically-confirmed epithelial ovarian cancer (EOC) - excluding low grade tumors and mucinous histology - and documented disease recurrence following primary or interval debulking surgery and 1-2 prior lines of chemotherapy (including a frontline platinum-based regimen) and a platinum-free interval greater than 6 months will be eligible to enroll in the study.

Twenty-four patients will be included in the study. The study diagram is shown in Figure 1 and the schedule of assessments (SoA) is shown in Section 6.0. After signing the informed consent, eligible subjects according to the inclusion and exclusion criteria will receive oral Lenvatinib 20 mg once daily (QD) plus intravenous (IV) pembrolizumab 200 mg every three weeks (Q3W) until evident progressive disease by CT (RECIST), or unacceptable toxicity, or until completion of 35 treatment cycles with pembrolizumab.

Disease status will be evaluated radiologically by computed tomography (CT) every 9 weeks, in comparison to pretreatment CT, until progression. In case of study withdrawal due to other reasons, radiological evaluation will be maintained every 9 weeks until disease progression or patient's withdrawal of consent or a new anticancer regimen is given. Patients with contrast media allergy will undergo chest CT without contrast medium as well as abdominal and pelvic magnetic resonance imaging (MRI).

Toxicity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Ver. 5.0 (NCI-CTCAE). Dose reductions and modification of Lenvatinib will be performed according to the indications in Section 5.2.3. Pembrolizumab dose will not be reduced but the dose can be delayed for up to 9 weeks in case of toxicity which requires steroid.

treatment and steroids withdrawal (refer to Section 5.2.2 on pembrolizumab dose interruptions). Refer to section 5.2.4 for dose modifications for overlapping toxicities.

Health-related quality of life will also be evaluated. Collateral research will focus on potential biomarkers of response to treatment and on micro- and macro-environmental changes occurring during the course of treatment. To that end, tumor biopsies, stool and vaginal swabs and blood (plasma, serum and peripheral blood mononuclear cells (PBMC)) samples will be collected at Screening and during the study. Analyses will be performed to determine pre- and post-treatment changes as well as differences between responders to treatment and non-responders.

Participants who stop study treatment after receiving 35 administrations of pembrolizumab for reasons other than disease progression or intolerability, or participants who attain a complete response (CR) and stop study treatment may be eligible for up to 1 year of treatment with pembrolizumab (17 cycles) ± Lenvatinib upon experiencing disease progression (Second Course Phase). Participants who complete treatment with pembrolizumab after 35 cycles (approximately 2 years) or CR will continue to receive Lenvatinib alone until disease progression, development of unacceptable toxicity, or withdrawal of consent.

Pembrolizumab and Lenvatinib for Platinum- Sensitive Recurrent Ovarian Cancer

A Phase II, Open Lable, Single Arm, Trial to Determine Efficacy and Safety of Lenvatinib in Combination With Pembrolizumab for Platinum- Sensitive Recurrent Ovarian Cancer

defined as the time from study treatment initiation to the first documented disease progression according to RECIST 1.1 or death from any cause.

defined as the percentage of evaluable patients with complete response (CR) or partial response (PR). Response will be evaluated by the Investigator according to RECIST 1.1.

defined as the time (in months) from initiation of treatment with pembrolizumab and Lenvatinib to subsequent chemotherapy treatment initiation.

defined as the time from study treatment initiation to death due to any cause.

To evaluate the impact of the treatment protocol on health-related quality of life (HR-QoL) as assessed by using the global score of the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Safety and tolerability assessed by CTCAE v5.0.

To evaluate the impact of the treatment protocol on health-related quality of life (HR-QoL) as assessed by using the ovarian cancer-specific protocol, (EORTC) QLQ-OV28 for participants treated with Lenvatinib in combination with pembrolizumab.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Sheba Medical Center

M.D, Head onco-gynecological service, Principal Investigator

Spots Global Cancer Trial Database for ovarian epithelial