A Phase III, Randomized, Double-blinded, Multicenter Study of AK105 Combined With Carboplatin and Pemetrexed vs Placebo Combined With Carboplatin and Pemetrexed as First-line Therapy in Patients With Metastatic Nonsquamous Non-small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- AK105
- Conditions
- Lung Cancer Non-small Cell Stage IV
- Sponsor
- Akeso
- Enrollment
- 164
- Locations
- 2
- Primary Endpoint
- Progression-free survival (PFS) in intent-to-treat (ITT) population, assessed by Independent Radiologist Review Committee(IRRC) in accordance with RECIST v1.1
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase III , randomized, double-blinded, multicenter clinical study to compare efficacy and safety of AK105 (Anti-PD1 antibody) combined with Carboplatin and Pemetrexed vs Placebo combined with Carboplatin and Pemetrexed as first-line therapy in patients with EGFR and ALK wild type metastatic nonsquamous non-small cell lung cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Expected life expectance ≥ 3 months.
- •Histologically or cytologically confirmed diagnosis of stage IV nonsquamous 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 \< 12 months prior to first dose of study treatment.
- •Subjects must provide wild-type EGFR and ALK reported by tissue-based tests. For subjects without documented wild-type EGFR/ALK, archival or fresh tumor tissues are required for EGFR/ALK assessment prior to enrollment.
- •Adequate organ function.
Exclusion Criteria
- •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.
Arms & Interventions
AK105 plus Carboplatin and Pemetrexed
Subjects receive AK105 200 mg intravenously (IV) plus pemetrexed 500 mg/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 plus pemetrexed 500 mg/m\^2 IV Q3W until progression.
Intervention: AK105
AK105 plus Carboplatin and Pemetrexed
Subjects receive AK105 200 mg intravenously (IV) plus pemetrexed 500 mg/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 plus pemetrexed 500 mg/m\^2 IV Q3W until progression.
Intervention: carboplatin
AK105 plus Carboplatin and Pemetrexed
Subjects receive AK105 200 mg intravenously (IV) plus pemetrexed 500 mg/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 plus pemetrexed 500 mg/m\^2 IV Q3W until progression.
Intervention: pemetrexed
Placebo plus Carboplatin and Pemetrexed
Subjects receive placebo intravenously (IV) plus pemetrexed 500 mg/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 plus pemetrexed 500 mg/m\^2 IV Q3W until progression.
Intervention: carboplatin
Placebo plus Carboplatin and Pemetrexed
Subjects receive placebo intravenously (IV) plus pemetrexed 500 mg/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 plus pemetrexed 500 mg/m\^2 IV Q3W until progression.
Intervention: pemetrexed
Placebo plus Carboplatin and Pemetrexed
Subjects receive placebo intravenously (IV) plus pemetrexed 500 mg/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 plus pemetrexed 500 mg/m\^2 IV Q3W until progression.
Intervention: placebo
AK105 plus anlotinib
Subjects receive AK105 200 mg intravenously (IV) plus Anlotinib 12mg/d PO D1-14, Q3W until progression.
Intervention: AK105
AK105 plus anlotinib
Subjects receive AK105 200 mg intravenously (IV) plus Anlotinib 12mg/d PO D1-14, Q3W until progression.
Intervention: Anlotinib
Outcomes
Primary Outcomes
Progression-free survival (PFS) in intent-to-treat (ITT) population, assessed by Independent Radiologist Review Committee(IRRC) in accordance with RECIST v1.1
Time Frame: up to 2 years
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).
Secondary Outcomes
- Disease control rate (DCR)(Up to 2 years)
- Incidence and severity of treatment-emergent adverse events (TEAEs)(From the time of informed consent signed through 90 days after last dose of AK105)
- PFS assessed by the investigator in accordance with RECIST v1.1(Up to 2 years)
- Objective response rate (ORR)(Up to 2 years)
- Overall survival (OS) in ITT population(Up to 2 years)
- Observed concentrations of AK105(From first dose of AK105 through 90 days after last dose of AK105)
- Duration of response (DoR)(Up to 2 years)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK105 through 90 days after last dose of AK105)