Study of Ociperlimab (BGB-A1217) in Combination With Tislelizumab in Advanced Solid Tumors

Sponsor

BeiGene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04047862

Collaborator

(none)

542

Enrollment

Locations

Arms

61.2

Anticipated Duration (Months)

8.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objectives of this study are : to assess the safety and tolerability, to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and to determine the recommended Phase 2 dose (RP2D) of BGB-A1217 (known as Ociperlimab) in combination with tislelizumab in participants with advanced solid tumors in phase 1.

Primary objective of Phase 1b is to assess overall response rate (ORR) determined by Investigator per RECIST v1.1 for patients in each dose- expansion cohort

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced and Metastatic Solid Tumors	Drug: Ociperlimab Drug: Tislelizumab Drug: Pemetrexed Drug: Paclitaxel Drug: Nab paclitaxel Drug: Carboplatin Drug: Cisplatin Drug: Etoposide Drug: 5fluorouracil Drug: Oxaliplatin Drug: Capecitabine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

542 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1/1b Study Investigating Safety, Tolerability, PK and Antitumor Activity of Anti-TIGIT Monoclonal Antibody BGB-A1217 in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

Actual Study Start Date :

Aug 26, 2019

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 Cycle 1 (28 Days): A flat dose of ociperlimab as a single agent on Day 1. In the first cycle, 200 mg tislelizumab will be administered on Day 8. If ociperlamib is tolerated in Cycle 1, participants will receive tislelizumab + ociperlimab sequentially on Day 29 and every 21 days for up to 8 months.	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection
Experimental: Phase 1b Cohort 1 Participants with metastatic squamous NSCLC will receive ociperlamib + tislelizumab + paclitaxel/nab-paclitaxel + Carbo once every 3 weeks (Q3W) for 4 to 6 cycles (21 days each) followed by ociperlimab + tislelizumab Q3W)	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection Drug: Paclitaxel Administered in accordance with local guidelines , prescribing information/summary of product Drug: Nab paclitaxel Administered in accordance with local guidelines , prescribing information/summary of product Drug: Carboplatin Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort 2 Participants with metastatic squamous NSCLC will receive ociperlimab + tislelizumab + pemetrexed + Cis/Carbo Q3W for 4 to 6 cycles (21 days each) followed by ociperlamib+tislelizumab Q3W)	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection Drug: Pemetrexed Administered in accordance with local guidelines, prescribing information/summary of product Drug: Carboplatin Administered in accordance with local guidelines , prescribing information/summary of product Drug: Cisplatin Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort 3 Participants with metastatic NSCLC (PD-L1 positive, [TC] ≥ 1%) will be treated with ociperlimab + tislelizumab	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection
Experimental: Phase 1b Cohort 4 Patients with extensive stage SCLC will be treated with ociperlimab + tislelizumab + etoposide + Cis/Carbo Q3W for up to 6 to 8 cycles followed by ociperlamib+tislelizumab Q3W	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection Drug: Carboplatin Administered in accordance with local guidelines , prescribing information/summary of product Drug: Cisplatin Administered in accordance with local guidelines , prescribing information/summary of product Drug: Etoposide Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort 5 Checkpoint inhibitor (CPI)-experienced NSCLC patients will be treated with ociperlimab plus tislelizumab	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection
Experimental: Phase1b Cohort 6 Patients with metastatic ESCC will be treated with ociperlimab + tislelizumab + cisplatin + 5-fluorouracil /paclitaxel Q3W for 6 cycles followed by ociperlamib+tislelizumab Q3W	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection Drug: Paclitaxel Administered in accordance with local guidelines , prescribing information/summary of product Drug: Cisplatin Administered in accordance with local guidelines , prescribing information/summary of product Drug: 5fluorouracil Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase1b Cohort 7 Patients with metastatic EAC will be treated with ociperlimab + tislelizumab + cisplatin + 5-fluorouracil or paclitaxel Q3W for 6 cycles followed by ociperlamib+tislelizumab Q3W	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection Drug: Paclitaxel Administered in accordance with local guidelines , prescribing information/summary of product Drug: Cisplatin Administered in accordance with local guidelines , prescribing information/summary of product Drug: 5fluorouracil Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase1b Cohort 8 Patients with recurrent or metastatic HNSCC (PD-L1 positive, vCPS≥ 1%) will be treated with ociperlimab + tislelizumab Q3W	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection
Experimental: Phase1b Cohort 9 Patients with metastatic G/GEJ carcinoma will be treated with ociperlimab + tislelizumab + [oxalipatin + capecitabine] or [cisplatin + 5-fluorouracil] Q3W for 6 cycles followed by ociperlamib+tislelizumab + capecitabine Q3W	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection Drug: Cisplatin Administered in accordance with local guidelines , prescribing information/summary of product Drug: 5fluorouracil Administered in accordance with local guidelines , prescribing information/summary of product Drug: Oxaliplatin Administered in accordance with local guidelines , prescribing information/summary of product Drug: Capecitabine Administered in accordance with local guidelines , prescribing information/summary of product
Experimental: Phase 1b Cohort10 Patients with metastatic NSCLC (PD-L1 positive, [TC] ≥ 1%) will be treated with tislelizumab in combination with ociperlimab 450mg, 900mg or 1800mg Q3W.	Drug: Ociperlimab Administered as an intravenous (IV) injection Drug: Tislelizumab Administered as an IV injection

Outcome Measures

Primary Outcome Measures

Phase 1 Dose Escalation - Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0) [Up to 28 Days in Cycle 1]
Phase 1 Dose Escalation - Number of participants experiencing Serious Adverse Events (SAEs) [Up to 1.5 years]
Phase 1 Dose Escalation - Recommended Phase Ib dose (RP2D) of ociperlimab in combination with tislelizumab [Up to 1.5 years]
Phase 1b Dose Confirmation - Anti-tumor activity of ociperlimab in combination with tislelizumab in patients with select advanced solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using RECIST v. 1.1. [Up to 1.5 years]

Secondary Outcome Measures

Duration of response (DOR) [Up to 3 years]
Duration of response (DOR) will be determined from investigator derived tumor assessments per RECIST v. 1.1.
Disease control rate (DCR) [Up to 3 years]
Disease control rate (DCR) will be determined from investigator derived tumor assessments per RECIST v. 1.1.
Progression free survival [Up to 3 years]
Progression free survival will be determined from investigator derived tumor assessments per RECIST 1.1.
Immunogenicity as assessed by the presence of anti-drug antibodies [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Phase 1 Key Inclusion Criteria

Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
≥ 1 measurable lesion per RECIST v1.1.
Has adequate organ function.
phase 1- Patients with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for which treatment is not available, not tolerated or refused.

Phase 1b Key Inclusion Criteria

Signed informed consent form (ICF) and able to comply with study requirements.
Age ≥ 18 years (or the legal age of consent) at the time the ICF is signed.
Histologically or cytologically confirmed tumor types in the following disease cohorts:

Cohort 1: stage IV squamous NSCLC Cohort 2: stage IV non-squamous NSCLC Cohort 3:

stage IV squamous or non-squamous NSCLC with PD-L1 positive. Cohort 4: extensive-stage SCLC Cohort 5: stage IIIB, IIIC or IV NSCLC Cohort 6: stage IV ESCC Cohort 7: stage IV

EAC Cohort 8: recurrent or metastatic HNSCC incurable by local therapies Cohort 9:

stage IV G/GEJ adenocarcinoma. Cohort 10: stage IV squamous or non-squamous NSCLC with PD-L1 positive.

ECOG Performance Status ≤ 1
Adequate organ function
Willing to use highly effective method of birth control

Phase 1 Key Exclusion Criteria:

Active brain or leptomeningeal metastasis.
Active autoimmune diseases or history of autoimmune diseases that may relapse.
With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
Concurrent participation in another therapeutic clinical trial.
Received prior therapies targeting TIGIT.

Phase 1b Key Exclusion Criteria:

Patients with any prior therapy for recurrent/metastatic disease.
Non-squamous NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion.
Gastric cancer patients with squamous or with positive HER2 expression.
Prior therapy with any drug specifically targeting T-cell co-stimulation or checkpoint pathways. (anti-PD(L)1 exception for Cohort 5).
Active leptomeningeal disease or uncontrolled brain metastasis.
Active autoimmune diseases or history of autoimmune diseases that may relapse.
With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
Concurrent participation in another therapeutic clinical study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Phoenix	Arizona	United States	85254
2	Genesis Care USA	Aventura	Florida	United States	33180
3	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
4	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
5	Sarah Cannon Research Institute (SCRI) Florida Cancer Specialist Panhandle	Tallahassee	Florida	United States	32308
6	Sarah Cannon Research Institute (SCRI)- Florida Cancer Specialist East	West Palm Beach	Florida	United States	33401
7	University of Kansas Medical Center Research Institute	Kansas City	Kansas	United States	66160
8	University of Minnesota	Minneapolis	Minnesota	United States	55455
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	Rutgers-Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
11	Montefiore Einstein Center for Cancer Care	Bronx	New York	United States	10461
12	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
13	Providence Portland	Portland	Oregon	United States	97213
14	UPMC Cancer Pavillion	Pittsburgh	Pennsylvania	United States	15232
15	Sarah Cannon Research Institute(SCRI)	Nashville	Tennessee	United States	37203
16	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
17	Blacktown Hospital	Blacktown	New South Wales	Australia	2146
18	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
19	Icon Cancer Foundation	South Brisbane	Queensland	Australia	4101
20	Metro South Health, Cancer Trials Unit Division of Cancer Services - PAH	Woolloongabba	Queensland	Australia	4102
21	Tennyson Centre Day Hospital	Adelaide	South Australia	Australia	5037
22	Adelaide Cancer Centre (Ashford Cancer Centre (ACC)) - 480 Specialist Centre	Adelaide	South Australia	Australia	5087
23	Southern Oncology Clinical Research Unit	Bedford Park	South Australia	Australia	5042
24	Royal Hobart Hospital (RHH)	Hobart	Tasmania	Australia	7000
25	Bendigo Health	Bendigo	Victoria	Australia	2550
26	Monash Hospital	Clayton	Victoria	Australia	3168
27	St Vincent's Hospital	Fitzroy	Victoria	Australia	3065
28	Linear Clinical Research	Perth	Western Australia	Australia	6009
29	St John of God - Subiaco Hospital - Bendat Family Comprehensive Cancer Centre (BFCCC)	Subiaco	Western Australia	Australia	6008
30	Chinese PLA General Hospital	Beijing	Beijing	China	100039
31	Beijing Cancer Hospital	Beijing	Beijing	China	100142
32	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150081
33	Henan Cancer Hospital	Zhengzhou	Henan	China
34	Hubei Cancer Hospital	Wuhan	Hubei	China	400037
35	Hunan Cancer Hospital	Changsha	Hunan	China	410013
36	Jilin Cancer Hospital	Changchun	Jilin	China	132000
37	Jinan Central Hospital	Jinan	Shandong	China	250013
38	Shandong provincial Qianfoshan Hospital	Jinan	Shandong	China
39	WeiFang People's Hospital	Weifang	Shandong	China	261000
40	The First Affiliated Hospital Of Xi'an Jiao Tong University	Xi'an	Shanxi	China	710061
41	Tianjin Medical University General Hospital	Tianjin	Tianjin	China	300052
42	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310022
43	Fujian Cancer Hospital	Fujian		China
44	Nanfang Hospital of Southern Medical University	Guangdong		China
45	Shanghai Chest Hospital	Shanghai		China
46	Tianjin Medical University Cancer Institute and Hospital	Tianjin		China	300060
47	National Cancer Center (NCC)	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
48	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
49	The Catholic University of Korea - St. Vincent's Hospital	Suwon	Gyeonggi-do	Korea, Republic of	16247
50	Gyeongsang National University Hospital	Jinju-si	Gyeongsangnam-do	Korea, Republic of	52727
51	The Catholic University of Korea - Seoul St. Mary's Hospital	Seoul	Recruiting	Korea, Republic of	06591
52	SMG-SNU Boramae Medical Center - Oncology	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp	Korea, Republic of	07061
53	Pusan National University Hospital	Busan		Korea, Republic of	49241
54	Gachon University (Gil Medical Center)	Incheon		Korea, Republic of	21565
55	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of
56	Auckland City Hospital	Auckland		New Zealand	1023
57	Christchurch Clinical Studies	Christchurch		New Zealand	8140
58	Buddhist Tzu Chi General Hospital - Hualien Tzu Chi Medical Center	Hualien City		Taiwan	970
59	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung City		Taiwan	833301
60	Chung Shan Medical University Hospital	Taichung		Taiwan	40201
61	China Medical University Hospital	Taichung		Taiwan	40447
62	Taichung Veterans General Hospital	Taichung		Taiwan	40705
63	National Taiwan University Hospital (NTUH)	Taipei		Taiwan	100225
64	Taipei Veterans General Hospital	Taipei		Taiwan	11217
65	Taipei Tzu Chi hospital, Buddhist Tzu Chi Medical Foundation	Taipei		Taiwan
66	Chang-Gung Memorial Hospital	Taoyuan		Taiwan	333
67	National Taiwan University Hospital (NTUH)	Zhongzheng		Taiwan	10002