A Study of BGB-A317 as Monotherapy in Relapsed or Refractory Classical Hodgkin Lymphoma

Study Description

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Brief Summary:

The study is to evaluate the efficacy of BGB-A317 assessed by Independent Review Committee (IRC) in subjects with relapsed or refractory classical Hodgkin lymphoma (cHL), as measured by Overall Response Rate (ORR) per the Lugano Classification

Condition or disease	Intervention/treatment	Phase
Classical Hodgkin Lymphoma	Drug: BGB-A317	Phase 2

Detailed Description:

This is an open-label, single-arm, multi-center and multi-national Phase 2 study.Approximately 68 with confirmed CHL would be enrolled.

Response will be assessed by computed tomography (CT) scan per the Lugano Classification. Computed tomography scan with contrast will occur as required by protocol, until progressive disease (PD), new anti-cancer therapy, withdrawal of consent, death, lost to follow-up, or end of study (EOS), whichever occurs first. Total body magnetic resonance imaging (MRI) is allowed if CT with contrast is contraindicated. Positron emission tomography (PET)/CT may be used in lieu of a CT with contrast only if the CT of the PET/CT has been performed with diagnostic quality and contrast is administered.

During treatment with immune checkpoint inhibitor such as with BGB-A317, pseudo-progression may occur due to immune cell infiltration and other mechanisms as manifested by apparent increase of existing tumor masses or appearance of new tumor lesions. Subjects are allowed to continue study treatment if there is suspicion of pseudo-progression, provided they are asymptomatic and have radiographic progression only, until a second consecutive CT scan demonstrates PD at which time study treatment will be discontinued permanently.

Subjects will be evaluated for AEs (all Grades per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 [NCI CTCAE v. 4.03]), serious AEs (SAEs), and any AEs requiring study drug interruption or discontinuation.

The Safety Population includes all subjects who received any dose of BGB-A317. This will be the population for the safety analyses. The modified Safety Population includes all subjects in the Safety Population who had confirmed cHL. This will be the population for the efficacy analyses.

The Per-protocol Population (PP) includes subjects who received any dose of BGB-A317 and had no major protocol deviations. Criteria for exclusion from the PP will be determined and documented before the database lock for the primary analysis. This will be the secondary analysis population for efficacy analysis. The PK population includes all subjects who whom valid BGB-A317 PK parameters can be estimated.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	68 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Single Arm, Multicenter, Phase 2 Study of BGB-A317 as Monotherapy in Relapsed or Refractory Classical Hodgkin Lymphoma
Actual Study Start Date :	April 21, 2017
Estimated Primary Completion Date :	August 2018
Estimated Study Completion Date :	January 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: BGB-A317; BGB-A317 200 mg intravenously (IV) every-3-weeks (Q3W)	Drug: BGB-A317; BGB-A317 200 mg intravenously (IV) every-3-weeks

Outcome Measures

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Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
   Overall Response Rate (ORR) defined as the proportion of subjects who achieves a best response of CR or PR, assessed by IRC per the Lugano Classification

Secondary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: Up to 2years ]
   From the first dose of BGB-A317 to the date of PD or death, whichever occurs first
2. Duration of Response (DOR) [ Time Frame: Up to 2 years ]
   From the date that response criteria are first met to the date that PD is objectively documented or death, whichever occurs first
3. Rate of CRR [ Time Frame: Up to 2 years ]
4. Time to Response (TTR) [ Time Frame: 2 years ]
   From the date of the first dose of BGB-A317 to the time the response criteria are first met

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. ≥ 18 years of age at time of informed consent.
2. Histologically confirmed relapsed or refractory cHL.
3. Subject must have relapsed (disease progression after most recent therapy) or refractory (failure to achieve CR/CMR or partial response [PR] to most recent therapy) cHL.
4. Subject must have measurable disease defined as ≥ 1 nodal lesion that is > 1.5 cm in the longest diameter, or ≥ 1 extra-nodal lesion (e.g. hepatic nodules) that is > 1 cm in the longest diameter.
5. Availability of archival or fresh tumor tissue sample from an evaluable core or excisional biopsy.
6. ECOG performance status of 0 or 1.
7. Life expectancy ≥ 12 weeks.
8. Subject must have adequate organ functions and meet requirements on laboratory values.
9. International normalized ratio (INR) ≤ 1.5 x ULN and aPTT ≤ 1.5 x ULN, unless patient is receiving anticoagulant therapy and coagulation parameters (PT/INR and aPTT,) are within intended therapeutic range of intended use of the anticoagulant at time of Screening.
10. Subject must have no evidence of dyspnea at rest and a pulse oximetry of > 92% while breathing room air.
11. Subject must have FEV1/ FVC > 60% by PFT, unless due to large mediastinal mass from HL; DLCO, FEV1 and FVC all > 50 % predicted value; all PFTs must be obtained within 4 weeks prior to the first dose of BGB-A317.
12. Female subject is eligible to enter and participate in the study if she is of a. Non-childbearing potential b. Childbearing potential and has a negative screening serum pregnancy test (within 3 days before the first dose of BGB-A317), not be breastfeeding, and agrees to use adequate contraception during the study treatment period and for at least 120 days after the last dose of BGB-A317. Adequate contraception, when used consistently and in accordance with both the product label and instructions of the physician.
13. Male subject is eligible if he is vasectomized or agrees to the use of contraception during the study treatment period and for at least 180 days after the last dose of BGB-A317.
14. Prior chemotherapy, radiotherapy, immunotherapy or investigational therapy (including Chinese herbal medicine and Chinese patent medicine) used to control cancer including locoregional treatment must have been completed ≥ 4 weeks before the first dose of BGB-A317, and all treatment-related adverse events (except alopecia) are stable and have either returned to baseline or Grade 0/1.
15. Subject has voluntarily agreed to participate by giving written informed consent.

Exclusion Criteria:

1. Nodular lymphocyte-predominant Hodgkin lymphoma or gray zone lymphoma.
2. Prior allogeneic hematopoietic stem cell transplant.
3. History of severe hypersensitivity reaction to monoclonal antibodies.
4. New York Heart Association (NYHA) class III or IV heart failure, unstable angina, severe uncontrolled ventricular arrhythmia, electrocardiographic evidence of acute ischemia, or myocardial infarction within 6 months of first day of Screening.
5. Prior malignancy within the past 3 years except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast.
6. Prior therapy targeting PD-1 or PD-L1.
7. Subject with active autoimmune disease or history of autoimmune disease with high risk of recurrence.
8. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily Prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of BGB-A317.
9. Has history of interstitial lung disease or non-infectious pneumonitis. Subjects with prior drug-induced or radiation-induced pneumonitis who are asymptomatic are eligible.
10. QTcF interval > 450 msec, unless secondary to bundle branch block.
11. Serious acute or chronic infection requiring systemic therapy.
12. Known CNS lymphoma.
13. Underlying medical conditions that, in the Investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
14. Known HIV, or active HBV or HCV infection.
15. Autologous hematopoietic stem cell transplant within 100 days of first dose of BGB-A317.
16. Use of any live vaccine against infectious diseases (e.g. influenza, varicella, etc.) within 4 weeks (28 days) of the first dose of BGB-A317, and any intended use within 60 days after the last dose of BGB-A317.
17. Major surgery within 4 weeks of the first dose of BGB-A317.
18. Pregnant or lactating women.

Contacts and Locations

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Contacts

Contact: Shijuan Bian	+86 10 5895 8000	ClinicalTrials@beigene.com

Locations

China, Beijing
Beijing Cancer Hospital	Recruiting
Beijing, Beijing, China, 100142
301 Hospital	Not yet recruiting
Beijing, Beijing, China, 100853
Contact: Jiang Cao 010-669371661 301jgb@sina.com
China, Fujian
Fujian Province Tumor Hospital	Not yet recruiting
Fujian, Fujian, China, 200120
China, Guangdong
San Yat-sen University Cancer Center	Not yet recruiting
Guangzhou, Guangdong, China, 510060
China, Henan
Henan Cancer Province	Not yet recruiting
Zhengzhou, Henan, China
China, Hubei
Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology	Not yet recruiting
Wuhan, Hubei, China
China, Jiangsu
Jiangsu Province Hospital	Not yet recruiting
Nanjing, Jiangsu, China
China, Jilin
The First Affilliated Hospital of Jilin University	Not yet recruiting
Changchun, Jilin, China
China, Shanghai
Fudan University Shanghai Cancer Center	Not yet recruiting
Shanghai, Shanghai, China
China, Shanxi
The 1st Affiliated Hospital of Xi'An Jiaotong University	Not yet recruiting
Xi'an, Shanxi, China
China, Sichuan
West China Hospital of Sichuan University	Not yet recruiting
Chengdu, Sichuan, China
China, Tianjin
CAMS&PUMC Institute of Hematology	Recruiting
Tianjin, Tianjin, China, 300020
Tianjin Medical Universtity Cancer Institute and Hospital	Not yet recruiting
Tianjin, Tianjin, China, 300060
China, Zhejiang
Zhejiang Cancer Hospital	Not yet recruiting
Hangzhou, Zhejiang, China
Korea, Republic of
Seoul National University Bundang Hospital	Not yet recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of
National Cancer Center	Not yet recruiting
Goyang-si, Korea, Republic of
Samsung Medical Center	Not yet recruiting
Seoul, Korea, Republic of

Sponsors and Collaborators

BeiGene

More Information

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Responsible Party:	BeiGene
ClinicalTrials.gov Identifier:	NCT03209973 History of Changes
Other Study ID Numbers:	BGB-A317-203
First Posted:	July 6, 2017
Last Update Posted:	July 6, 2017
Last Verified:	July 2017

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms	Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases