A Study of AK104/Tislelizumab With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer

• Sponsor: Akeso (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05990127
• Collaborator: (none)
• Enrollment: 642
• Locations: 62
• Arms: 2
• Anticipated Duration (Months): 36.5
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, phase III clinical study to compare the efficacy and safety of AK104 combined chemotherapy versus Tislelizumab combined chemotherapy in first-line treatment of Locally advanced or metastatic NSCLC with PD-L1 TPS < 1%.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced or Metastatic NSCLC	Drug: AK104; Drug: Tislelizumab; Drug: carboplatin; Drug: Pemetrexed; Drug: Paclitaxel	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 642 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Phase III Trial to Compare the Efficacy and Safety of AK104 Combined With Chemotherapy to Tislelizumab Combined With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer (NSCLC)
• Anticipated Study Start Date: Nov 14, 2023
• Anticipated Primary Completion Date: Aug 5, 2025
• Anticipated Study Completion Date: Nov 28, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AK104 arm	Drug: AK104; AK104 IV, q3w; Drug: carboplatin; carboplatin IV, q3w; Drug: Pemetrexed; Pemetrexed IV, q3w (for Nonsquamous NSCLC); Drug: Paclitaxel; Paclitaxel IV, q3w (for squamous NSCLC)
Active Comparator: Tislelizumab arm	Drug: Tislelizumab; Tislelizumab IV, q3w; Drug: carboplatin; carboplatin IV, q3w; Drug: Pemetrexed; Pemetrexed IV, q3w (for Nonsquamous NSCLC); Drug: Paclitaxel; Paclitaxel IV, q3w (for squamous NSCLC)

Outcome Measures

Primary Outcome Measures

1. Overall Survival(OS) [Through Database Cutoff Date (Up to approximately 39 months)]

   OS is defined as the time from randomization to death due to any cause.

2. Progression-Free Survival(PFS) by investigator(INV) [Through Database Cutoff Date (Up to approximately 39 months)]

   PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1

Secondary Outcome Measures

1. Progression-Free Survival(PFS) by Blind independent center review(BIRC) [Through Database Cutoff Date (Up to approximately 39 months)]

   PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1

2. Objective response rate (ORR) was assessed by INV [Through Database Cutoff Date (Up to approximately 39 months)]

   ORR is the proportion of subjects with CR or PR based on RECIST v1.1

3. Disease control rate (DCR) was assessed by INV [Through Database Cutoff Date (Up to approximately 39 months)]

   Disease control rate (DCR) was assessed based on RECIST V1.1 criteria

4. Time to response (TTR) was assessed by INV [Through Database Cutoff Date (Up to approximately 39 months)]

   The time from the first administration to the date of documented CR or PR

5. Duration of response (DOR) was assessed by INV [Through Database Cutoff Date (Up to approximately 39 months)]

   Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria

6. Objective response rate (ORR) was assessed by BIRC [Through Database Cutoff Date (Up to approximately 39 months)]

   ORR is the proportion of subjects with CR or PR based on RECIST v1.1

7. Disease control rate (DCR) was assessed BIRC [Through Database Cutoff Date (Up to approximately 39 months)]

   Disease control rate (DCR) was assessed based on RECIST V1.1 criteria

8. Time to response (TTR) was assessed by BIRC [Through Database Cutoff Date (Up to approximately 39 months)]

   The time from the first administration to the date of documented CR or PR

9. Duration of response (DOR) was assessed by BIRC [Through Database Cutoff Date (Up to approximately 39 months)]

   Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria

10. The number of subjects experiencing adverse events (AEs) [Through Database Cutoff Date (Up to approximately 39 months)]

    Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.

11. Pharmacokinetic [Through Database Cutoff Date (Up to approximately 39 months)]

    The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration

12. Antidrug antibodies (ADA) of AK104 [Through Database Cutoff Date (Up to approximately 39 months)]

    Proportion of subjects who develop detectable anti-drug antibodies (ADAs)

13. Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [Through Database Cutoff Date (Up to approximately 39 months)]

    EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much". Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.

14. Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29) [Through Database Cutoff Date (Up to approximately 39 months)]

    EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much". For symptoms scales, higher scores indicated greater symptom burden.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The subjects voluntarily participated in the study with full informed consent and signed written informed consent form.

2. Aged ≥18 years when the subject signed the informed consent.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Life expectancy ≥ 3 months.

5. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) that not amenable to complete surgical resection and not amenable to radical concurrent/sequential chemoradiation or metastatic (Stage IV) NSCLC (American Joint Committee on Cancer [AJCC] 8th edition).

6. No prior systemic therapy for advanced or metastatic NSCLC was received.

7. PD-L1 TPS < 1%.

8. No EGFR sensitive mutations or ALK gene translocation alterations.

Exclusion Criteria:

1. Histologically confirmed small cell lung cancer (SCLC).

2. NSCLC with driver gene mutations for approved targeted drug indications.

3. Active central nervous system (CNS) metastases were present.

4. Pulmonary radiation therapy > 30 Gy within 6 months prior to first dose.

5. Active malignant tumors within the past 5 years, except for tumors in this study and scured local tumors.

6. Pregnant or lactating women.

7. Clinically significant cardiovascular or cerebrovascular disease.

8. Subjects with a known history of severe hypersensitivity to other monoclonal antibodies. A known history of allergy or hypersensitivity to all investigational drugs or any of their components.

9. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or autoimmune diseases that may relapse or require scheduled treatment as judged by the Investigator.

10. Known active pulmonary tuberculosis.

11. Patients with active hepatitis B or active hepatitis C.

12. Known medical history of immunodeficiency or positive HIV test.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The first affiliated hospital of bengbu medical college	Bengbu	Anhui	China	233099
2	Anhui provincial hospital	Hefei	Anhui	China	230001
3	Anhui provincial cancer hospital	Hefei	Anhui	China	230088
4	The first affiliated hospital of wannan medical college	Wuhu	Anhui	China	241001
5	Cancer hospital, Chinese academy of medical sciences and Peking union medical college	Beijing	Beijing	China	100021
6	The Fifth Medical Center of the Chinese People's Liberation Army General Hospital	Beijing	Beijing	China	100039
7	Beijing Cancer Hospital	Beijing	Beijing	China	100142
8	Beijing Chest hospital	Beijing	Beijing	China	101149
9	Chongqing University Cancer Hospital	Chongqing	Chongqing	China	400030
10	Fujian cancer hospital	Fuzhou	Fujian	China	350014
11	Zhangzhou municipal hospital of fujian province	Zhangzhou	Fujian	China	363099
12	Gansu provincial cancer hospital	Lanzhou	Gansu	China	730050
13	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510080
14	Affiliated cancer hospital and institute of guangzhou medical university	Guangzhou	Guangdong	China	510095
15	Nanfang hospital	Guangzhou	Guangdong	China	510515
16	Cancer hospital Chinses academy of medical sciences， shenzhen center	Shenzhen	Guangdong	China	518172
17	Hainan cancer hospital	Haikou	Hainan	China	570312
18	Affiliated hospital of Hebei university	Baoding	Hebei	China	050031
19	The second people's hospital of Hengshui	Hengshui	Hebei	China	053099
20	The Second Hospital of HeBei Medical University	Shijiazhuang	Hebei	China	050004
21	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050011
22	Tangshang people's hospital	Tangshan	Hebei	China	063001
23	Harbin medical university cancer hospital	Harbin	Heilongjiang	China	150081
24	Jiamusi Tuberculosis Prevention and Control Hospital (Jiamusi Cancer Hospital)	Jiamusi	Heilongjiang	China	154007
25	The first hospital of Qiqihar	Qiqihar	Heilongjiang	China	161005
26	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan	China	450052
27	Nanyang central hospital	Nanyang	Henan	China	473005
28	The First Affiliated Hospital of Xinxiang Medical College	Xinxiang	Henan	China	45310
29	Henan Cancer Hospital	Zhengzhou	Henan	China	450003
30	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450052
31	Renmin Hospital of Wuhan University	Wuhan	Hubei	China	430060
32	Hubei Cancer Hospital	Wuhan	Hubei	China	430079
33	Xiangya Hospital of Central South University	Changsha	Hunan	China	410008
34	The Second Xiangya Hospital, Central South University	Changsha	Hunan	China	410012
35	Hunan Cancer Hospital	Changsha	Hunan	China	410013
36	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215006
37	The affiliated hospital of xuzhou medical university	Xuzhou	Jiangsu	China	221799
38	First Affiliated Hospital of Gannan medical college	Ganzhou	Jiangxi	China	341000
39	First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330006
40	The first hospital of Jilin Universit	Changchun	Jilin	China	130061
41	Tonghua Central Hospital	Tonghua	Jilin	China	134099
42	The First Hospital of China medical University	Shenyang	Liaoning	China	110002
43	Liaoning cancer hospital	Shenyang	Liaoning	China	110801
44	General hospital of ningxia medical university	Yinchuan	Ningxia	China	750003
45	Qinghai university affiliated hospital	Xining	Qinghai	China	810012
46	Binzhou medical university hospital	Binzhou	Shandong	China	256603
47	Shandong Cancer Hospital	Jinan	Shandong	China	250117
48	The Affiliated Hospital of Qingdao University	Qingdao	Shandong	China	266000
49	Weifang NO.2 people's Hospital	Weifang	Shandong	China	261041
50	Zhongshan Hospital, Fudan university	Shanghai	Shanghai	China	200032
51	Changzhi people's hospital	Changzhi	Shanxi	China	046099
52	Shanxi Cancer hospital	Taiyuan	Shanxi	China	030013
53	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi	China	710061
54	Sichuan Cancer Hospital	Chengdu	Sichuan	China	610042
55	Mianyang central hospital	Mianyang	Sichuan	China	621099
56	The Second People's Hospital of Yibin City	Yibin	Sichuan	China	644000
57	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin	China	300060
58	Tianjin Chest Hospital	Tianjin	Tianjin	China	300222
59	Xinjiang Medical University Cancer Hospital	Urumqi	Xinjiang	China	830000
60	Yunnan Cancer Hospital /the Third Affiliated Hospital of Kunming Medical University	Kunming	Yunnan	China	650118
61	The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU)	Hangzhou	Zhejiang	China	310003
62	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310005

Sponsors and Collaborators

• Akeso

Investigators

• Principal Investigator: Jie Wang, M.D., Cancer hospital, Chinese academy of medical sciences and Peking union medical college
• Principal Investigator: Qingming Wang, Henan Cancer Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Akeso
• ClinicalTrials.gov Identifier: NCT05990127
• Other Study ID Numbers: AK104-307
• First Posted: Aug 14, 2023
• Last Update Posted: Aug 14, 2023
• Last Verified: Aug 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Paclitaxel; Carboplatin; Pemetrexed; Tislelizumab

Study Results

No Results Posted as of Aug 14, 2023