A Study of Anti-PD-1 AK105 in Patients With Metastatic Squamous Non-small Cell Lung Cancer

NCT03866993 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: AK105-302
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase III, randomized, double-blinded, multicenter clinical study to evaluate the efficiency and safety of AK105 (Anti-PD1 antibody) plus paclitaxel and carboplatin vs placebo plus paclitaxel and carboplatin as First-line Therapy in patients with metastatic squamous non-small cell lung cancer.

Conditions

Lung Cancer Non-small Cell Stage IV; Squamous Cell Lung Cancer

Keywords

immuno-oncology; NSCLC; Anti-PD-1 Antibody; immunotherapy

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS) in intent-to-treat (ITT) population, assessed by Independent Radiologist Review Committee(IRRC) in accordance with RECIST v1.1

  PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by IRRC or death due to any cause (whichever occurs first).

  Up to approximately 2 years

• PFS in PD-L1-selected population, assessed by IRRC in accordance with RECIST v1.1

  PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by IRRC or death due to any cause (whichever occurs first).

  Up to approximately 2 years

Secondary Outcomes (9)

• Overall survival (OS) in ITT population

  Up to approximately 2 years

• Overall survival (OS) in PD-L1-selected population

  Up to approximately 2 years

• PFS assessed by the investigator in accordance with RECIST v1.1

  Up to approximately 2 years

• Objective Response Rate (ORR)

  Up to approximately 2 years

• Duration of response (DoR)

  Up to approximately 2 years

Study Arms (2)

AK105 plus Carboplatin and Paclitaxel

EXPERIMENTAL

Subjects receive AK105 200 mg intravenously (IV) plus Paclitaxel 175mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK105 200 mg IV Q3W until progression.

Biological: AK105; Drug: Paclitaxel; Drug: Carboplatin

placebo plus Carboplatin and Paclitaxel

PLACEBO COMPARATOR

Subjects receive placebo intravenously (IV) plus Paclitaxel 175mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK105 200 mg IV Q3W until progression.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Placebo

Interventions

AK105 BIOLOGICAL

IV infusion

AK105 plus Carboplatin and Paclitaxel

Paclitaxel DRUG

IV infusion

AK105 plus Carboplatin and Paclitaxel; placebo plus Carboplatin and Paclitaxel

Carboplatin DRUG

IV infusion

AK105 plus Carboplatin and Paclitaxel; placebo plus Carboplatin and Paclitaxel

Placebo DRUG

IV infusion

placebo plus Carboplatin and Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent form voluntarily.
• Age over 18 years old (inclusive) and not more than 75 years old (inclusive), when signing the ICF.
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Expected life expectance ≥ 3 months.
• Histologically or cytologically confirmed diagnosis of stage IV squamous NSCLC.
• No prior systemic chemotherapy for advanced or metastatic NSCLC. Subjects who have received prior adjuvant chemotherapy or neoadjuvant chemotherapy with curative intent, or definitive chemoradiotherapy for advanced disease, will be eligible provided that progression has occurred \>6 months from last treatment.
• At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously irradiated will not be considered a target lesion.
• Subjects must provide an available tumor tissue sample taken \< 6 months prior to first dose of study treatment.
• Adequate organ function.
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception.
• Nonsterilized males who are sexually active with a female partner of childbearing potential must use highly effective method of contraception from Day 1 and for 120 days after the last dose of investigational product.

You may not qualify if:

• Subjects who are diagnosed as NSCLC that harbors an EGFR-sensitizing mutation or ALK gene translocation.
• Subjects with other histological types of NSCLC, including mixed squamous cell carcinoma and adenocarcinoma, and mixed carcinoma containing small cell lung carcinoma or neuroendocrine carcinoma.
• Received prior treatment with EGFR inhibitors or ALK inhibitors.
• Receipt of last radiotherapy or any anti-tumor treatment \[chemotherapy, targeted therapy, immunotherapy, Chinese patent drugs with antitumor indications, or immunomodulators or tumor embolization\] within 3 weeks prior to the first dose of study treatment.
• Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g. CD40, CD137, GITR and OX40 etc).
• Other invasive malignancies within 5 years, except for locally treatable (manifested as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
• Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with the exceptions of the following: vitiligo, alopecia, Grave disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of hormone replacement therapy and type I diabetes only requiring steady doses of insulin replacement therapy, or completely relieved childhood asthma that requires no intervention in adulthood, or primary diseases that will not relapse unless triggered by external factors.
• Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
• Subjects who require systemic corticosteroids (a dose equivalent to \>10 mg/day prednisone) or other immunosuppressive drugs within 14 days prior to the first dose of study drug.
• Major surgery (as defined by the investigator) within 28 days prior to the first dose of study drug.
• Subjects who received non-thoracic radiotherapy \>30 Gy within 4 weeks prior to the first dose, or thoracic radiotherapy \>30 Gy within 24 weeks prior to the first dose study drug.
• History of gastrointestinal perforation and/ or fistula within 6 months prior to the first dose of study drug.
• Known history of primary immunodeficiency virus infection.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known history of interstitial lung disease.

Sponsors & Collaborators

• Akeso: lead
• Akeso Tiancheng, Inc: collaborator

Study Sites (2)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200025, China

Location

Chinese PLA General Hospital

Beijing, China

Location

Related Publications (1)

• Zhong H, Sun S, Chen J, Wang Z, Zhao Y, Zhang G, Chen G, Zhou M, Zhou J, Du Y, Wu L, Xu Z, Mei X, Zhang W, He J, Cui J, Zhang Z, Luo H, Liu W, Sun M, Wu J, Shen Y, Zhang S, Yang N, Wang M, Lu J, Li K, Yao W, Sun Q, Yue H, Wang L, Ye S, Li B, Zhuang X, Pan Y, Zhang M, Shu Y, He Z, Pan L, Ling Y, Liu S, Zhang Q, Jiao S, Han B. First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial. Lancet Respir Med. 2024 May;12(5):355-365. doi: 10.1016/S2213-2600(23)00431-9. Epub 2024 Jan 31.

  PMID: 38309287 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Shunchang Jiao, MD

  Chinese PLA General Hospital

  STUDY CHAIR

• Baohui Han, MD

  Shanghai Chest Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: March 7, 2019
• Study Start: December 20, 2018
• Primary Completion: October 8, 2020
• Study Completion: January 14, 2022
• Last Updated: April 3, 2024

Record last verified: 2024-04

Locations

CN (2)