A Multicenter, Open-Label, Phase Ib/II Study of AK119 and AK112 With or Without Chemotherapy in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Akeso
- Enrollment
- 59
- Locations
- 1
- Primary Endpoint
- Number of subjects with dose limiting toxicities (DLTs)
Overview
Brief Summary
This is a phase Ib/II study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of AK119 and AK112 With or Without Chemotherapy for NSCLC patients.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Be able to understand and voluntarily sign the written informed consent, which must be signed before the designated research procedure.
- •Age ≥ 18 and ≤ 75, male or female.
- •Local advanced or metastatic non-squamous NSCLC confirmed by histology or cytology according to eighth edition of the TNM classification for lung cancer.
- •EGFR activating mutation confirmed by tumor histology, cytology or hematology.
- •Failed to previous EGFR-TKI treatment.
- •ECOG performance status 0 to
- •Life expectancy ≥3 months.
- •At least one measurable lesion according to RECIST v1.
- •Adequate organ function.
Exclusion Criteria
- •Histological or cytological pathology confirmed the presence of small cell carcinoma or squamous cell carcinoma.
- •Have suffered from the second primary active malignant tumor in the past 3 years.
- •There are other driving gene mutations that can obtain effective treatment.
- •Receipt of the following treatments or procedures: immunotherapy, including immunocheckpoint inhibitors, immunocheckpoint agonists, immunocellular therapy, and any other treatment targeting tumor immune mechanism; systematic chemotherapy in the advanced stage (IIIB-IV); anti-angiogenesis drugs, except for small molecule anti-angiogenesis drugs with drug withdrawal more than 4 weeks; extensive radiotherapy within 4 weeks; EGFR-TKIs within 2 weeks.
- •Symptomatic central nervous system metastases.
- •The toxicity of previous anti-tumor therapy has not been alleviated.
- •Uncontrolled massive ascites, pleural effusion or pericardial effusion.
- •Active autoimmune diseases in the past 2 years.
- •History of interstitial lung disease or noninfectious pneumonitis.
- •Suffering from clinically significant cardiovascular or cerebrovascular diseases.
Arms & Interventions
AK119 + AK112
Subjects will receive AK119 plus AK112 via intravenously (IV) Q3W, up to 2 years.
Intervention: AK119 (Drug)
AK119 + AK112
Subjects will receive AK119 plus AK112 via intravenously (IV) Q3W, up to 2 years.
Intervention: AK112 (Drug)
AK119 + AK112 + Pemetrexed + Carboplatin
Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
Intervention: AK119 (Drug)
AK119 + AK112 + Pemetrexed + Carboplatin
Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
Intervention: AK112 (Drug)
AK119 + AK112 + Pemetrexed + Carboplatin
Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
Intervention: Pemetrexed (Drug)
AK119 + AK112 + Pemetrexed + Carboplatin
Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
Intervention: Carboplatin (Drug)
AK112
Subjects will receive AK112 monotherapy via intravenously (IV) Q3W, up to 2 years.
Intervention: AK112 (Drug)
Outcomes
Primary Outcomes
Number of subjects with dose limiting toxicities (DLTs)
Time Frame: During the first 3 weeks
DLTs will be assessed during the first 3 weeks of treatment. DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the DLT observation period.
Number of subjects with adverse events (AEs)
Time Frame: From the time of informed consent signed through 90 days after the last dose of study drug
AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment.
Objective response rate (ORR)
Time Frame: Up to 2 years
ORR is defined as the proportion of subjects with confirmed CR or confirmed PR.
Secondary Outcomes
- Time to response (TTR)(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Maximum observed concentration (Cmax) of AK119 and AK112(From first dose of study drug through last dose)
- Disease control rate (DCR)(Up to 2 years)
- Duration of response (DoR)(Up to 2 years)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of study drug through last dose)