A Study of AK112 Combined With PARP Inhibitor in the Treatment of Recurrent Ovarian Cancer

NCT04999605 | Terminated Phase 1

• 1 other identifier: AK112-204
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Phase Ib/II open label, multicenter study to evaluate the efficacy and safety of anti-PD-1 and VEGF bispecific antibody (AK112) combined with PARP inhibitor in patients with recurrent ovarian cancer.

Conditions

Ovarian Neoplasms; Recurrent Ovarian Carcinoma; Relapsed Ovarian Cancer; Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Safety endpoint: number of subjects with adverse events (AE)

  An AE is any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

  Up to approximately 2 years

• Primary efficacy endpoint: objective response rate (ORR)

  ORR is the proportion of subjects with complete response(CR) or partial response(PR) assessed according to RECIST v1.1

  Up to approximately 2 years

Secondary Outcomes (8)

• Efficacy Endpoint assessed according to RECIST v1.1 : disease control rate (DCR)

  Up to approximately 2 years

• Efficacy Endpoint assessed according to RECIST v1.1 : progression-free survival (PFS)

  Up to approximately 2 years

• Efficacy Endpoint assessed according to RECIST v1.1 : Overall survival (OS)

  Up to approximately 2 years

• Serum PK concentrations of AK112

  Up to approximately 2 years

• To evaluate the immunogenicity of AK112: Number of subjects with anti-drug antibodies (ADA)

  Up to approximately 2 years

Study Arms (1)

AK112

EXPERIMENTAL

AK112 injection

Drug: AK112 low dose; Drug: AK112 medium dose; Drug: AK112 high dose

Interventions

AK112 low dose DRUG

AK112 injection low dose+ olaparib (Lynparza®) PARP inhibitor

AK112

AK112 medium dose DRUG

AK112 injection medium dose+ olaparib (Lynparza®) PARP inhibitor

AK112

AK112 high dose DRUG

AK112 injection high dose+ olaparib (Lynparza®) PARP inhibitor

AK112

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able and willing to provide written informed consent.
• ≥ 18 years old to ≤ 75 years old at study enrollment, female subjects.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have a life expectancy of at least 3 months.
• Have histologically or cytologically diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
• Have received at least two lines of platinum-containing treatment (bevacizumab or its biosimilars was allowed), and were platinum-sensitive recurrence (progression more than 6 months after the last dose of platinum-containing regimen).
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 assessed by investigator.
• Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue.
• Has adequate organ function.
• All subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
• Able to to comply with all requirements of study participation (including all study procedures).

You may not qualify if:

• Previous history (within five years) or concurrent malignant neoplasm, except that basal cell carcinoma and/or squamous cell carcinoma of the skin, superficial bladder cancer, cervical cancer in situ or breast cancer in situ that has undergone curative therapy.
• Participation in a study of an investigational drug or using an investigational device within 4 weeks of first study drug administration.
• Ovarian, fallopian tube or primary peritoneal cancer cancer of non-epithelial origin (such as germ cell carcinoma).
• Previous targeted therapy using small molecules (except PARP inhibitors) and/or immunotherapy.
• Have a potent or moderate CYP3A inhibitor, or a potent or moderate CYP3A inducer within 1 week prior to first study drug administration (or 5 drug half-lives, whichever is longer).
• Has an 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.
• Active or previous history of inflammatory bowel disease such as Crohn's disease, ulcerative colitis or chronic diarrhea.
• History of immunodeficiency and/or HIV antibody positive subjects.
• Has severe infection 4 weeks prior to first study drug administration, including but not limited to complications requiring hospitalization, sepsis or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks prior to first study drug administration (excluding antiviral therapy for hepatitis B or C).
• Has known active Hepatitis B that is untreated and requiring antiviral therapy during study period; or active Hepatitis C subjects (HCV antibody positive with HCV-RNA levels above the detection threshold).
• Has undergone major surgery or severe trauma within 30 days prior to the first study drug administration.
• Has known active central nervous system (CNS) metastases.
• Uncontrolled co-morbidities including but not limited to symptomatic congestive heart failure (NYHA≥2), unstable angina, acute myocardial infarction, poorly controlled arrhythmias, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe peptic ulcer disease or gastritis.
• Uncontrolled hypertension despite optimal medical treatment; history of hypertensive crisis or hypertensive encephalopathy.
• Any arterial thromboembolism, transient ischemic attack, cerebrovascular accident occurred within 6 months prior to the first study drug administration.

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100000, China

Location

MeSH Terms

Conditions

Ovarian Neoplasms

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 Officials

• Lingying Wu, MD

  Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: August 11, 2021
• Study Start: June 24, 2021
• Primary Completion: June 10, 2022
• Study Completion: June 10, 2022
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)