Acalabrutinib (ACP-196) Alone and in Combination With Pembrolizumab in Ovarian Cancer (KEYNOTE191)

Study Overview
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Brief Summary
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To characterize the safety and efficacy of acalabrutinib (ACP-196) monotherapy and acalabrutinib plus pembrolizumab combination therapy in subjects with recurrent ovarian cancer

Official Title
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A Phase 2 Proof-of-Concept Study of ACP-196 Alone and in Combination With Pembrolizumab in Subjects With Recurrent Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Acalabrutinib
* Drug: acalabrutinib and pembrolizumab combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥ 18 years of age. Histologically confirmed ovarian epithelial (including fallopian tube and primary peritoneal) carcinoma. Progression of disease after the most recent anticancer treatment. At least 1 prior chemotherapy regimen must have included a taxane. Platinum-sensitive ovarian cancer defined by recurrence or progression of disease > 6 AND < 24 months after completion of the most recent platinum-based therapy. Measurable disease as defined by RECIST 1.1. ECOG performance status of 0 or 1. Completion of all therapy for the treatment of cancer 2 weeks before the start of study therapy and recovered. Exclusion Criteria: Evidence of platinum-refractory ovarian cancer defined as recurrence or progression during the first 6 cycles of or < 6 months after the beginning of first-line platinum based chemotherapy. Evidence of platinum-resistant ovarian cancer defined as recurrence or progression within 6 months after completing the most recent platinum-based therapy. More than 3 prior lines of cytotoxic chemotherapy for ovarian cancer. Prior malignancy (other than ovarian cancer), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 2 years. Breastfeeding and pregnant. Known central nervous system metastases and/or carcinomatous meningitis. Subjects with active cardiovascular disease not medically controlled or those who have had myocardial infarction in the past 6 months.. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen 1<br>Drug: acalabrutinib monotherapy | Drug: Acalabrutinib<br> <br> * Other names: ACP-196;|
| Experimental: Regimen 2<br>Drug: Combination of acalabrutinib and pembrolizumab | Drug: acalabrutinib and pembrolizumab combination<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Every 12 weeks for up to 2 years. |