Non-Small Cell Lung Cancer With EGFR-mutated and PD-L1 Positive
Conditions
Brief summary
This is a phase 2, open-Label study to evaluate the efficacy and safety of ABSK043 Combined with Osimertinib in participants with EGFR-Mutated locally advanced or metastatic Non-Small Cell Lung Cancer
Detailed description
This is an open-label study with an escalation part and an expansion part. The dose escalation part will evaluate the safety, tolerability of ABSK043 in combination with Osimertinib in previously treated participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC. The expansion part will evaluate the efficacy of ABSK043 in combination with Osimertinib as first-line treatment for participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC at the one or more recommended dose(s). The safety, tolerability, and PK profile of ABSK043 in combination with Osimertinib will also be further evaluated. Escalation Part: The escalation part includes dose escalation cohorts and backfill cohort(s), enrolling a sufficient number with previously treated participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC. Expansion Part: The expansion part will enroll a sufficient number with treatment-naïve participants with locally advanced or metastatic NSCLC harboring the EGFR mutation and PD-L1 positive expression.
Interventions
DRUGABSK043 in combination with Osimertinib
Three potential dose levels of ABSK043 are prespecified, and Osimertinib will be administered orally at a fixed dose of 80 mg QD in escalation cohort. Patients in dose confirmation cohort and dose expansion cohort will receive the recommended dose in dose escalation cohort and be evaluated for safety and preliminary anti-tumor activity of the combination therapy.
Sponsors
Abbisko Therapeutics Co, Ltd
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
： 1. Aged 18 or above, male or female. 2. Participants must understand and voluntarily participate in this study and must have been provided informed consent for study participation. 3. NSNLC confirmed by tissue or cytological pathology. NSCLC with a mixed histology is eligible, if adenocarcinoma is the predominant histology. 4. Diagnosed locally advanced or metastatic NSCLC 5. Different requirements for specific cohort: Dose escalation and backfill cohorts: 1. Participants with disease in the adjuvant setting, post chemoradiotherapy setting, locally advanced stage or metastatic stage, who have received at least one prior line of third-generation EGFR-TKI-based monotherapy or combination therapy and experienced disease progression. 2. Participants must have received ≥2 prior lines of frontline systemic therapy. 3. Documented or central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%). 4. Documented genetic testing report confirms the presence of EGFR alteration(s) in tumor or plasma. Expansion cohort(s): 1. Participants must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting for locally advanced or metastatic disease. 2. Central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%). 3. Documented genetic testing reports confirm the presence of EGFR 6. Presence of at least one measurable tumor lesion 7. ECOG score 0-1 at screening. 8. The expected life expectancy after the first dose is \>12 weeks.
Exclusion criteria
* 1\. Histological or cytological examinations suggest that NSCLC squamous cells is the predominant histology, or contains small cell lung cancer, neuroendocrine carcinoma, etc. 2\. Has a history of interstitial lung disease (ILD)/pneumonitis or active ILD 3. Spinal cord compression and unstable brain metastases. 4.Any unresolved toxicities from prior systemic therapy greater than CTCAE v6.0 Grade 1 at the time of starting study treatment. 5\. Participants with obvious and unstable pleural effusion, peritoneal effusion or pericardial effusion . 6\. Has a history of other malignant tumors, or currently have other malignant tumors. 7\. Participants with known HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| - Incidence of dose-limiting toxicity (DLT) | At the end of Cycle 1 (each cycle is 21 days) | Escalation Part |
| Adverse events(AEs) | From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months. | Escalation Part |
| Serious adverse events (SAEs) | From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months. | Escalation Part |
| Adverse events of special interest (AESIs) | From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months. | Escalation Part |
| Progression-free survival at 12 month | From the time patients receive the first dose of study drug to 12 months，assessed up to 5 years. | Expansion Part |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration（Cmax） | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Area under the concentration-time curve area under the concentration-time curve area under the concentration-time curve (AUC) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Elimination half-life(t1/2) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Apparent volume of distribution(Vz/F) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Apparent oral clearance(CL/F) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Maximum observed concentration after multiple doses(Cmax,ss) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Minimum observed concentration after multiple doses(Cmin,ss) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Area under the concentration-time curve after multiple doses(AUCtau,ss) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Accumulation ratio(AR) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Time to maximum observed concentration(tmax) | From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months. | Escalation Part |
| Progression-Free Survival (PFS) | From treatment start up to 5 years | Escalation Part |
| Objective response rate (ORR) | From treatment start up to 5 years | Defined as the proportion of participants achieving confirmed complete response (CR) or partial response (PR), as assessed by the investigator according to RECIST v1.1. |
| Duration of response (DOR) | From treatment start up to 5 years | Defined as the time (months) from the first documented objective response to the investigator-assessed radiographic disease progression (PD) according to RECIST v1.1 or death from any cause, whichever occurs first. |
| Disease control rate (DCR) | From treatment start up to 5 years | Defined as the proportion of participants achieving confirmed complete remission (CR) or partial remission (PR), or stable disease (SD), as assessed by the investigator according to RECIST v1.1. |
| Time to progression (TTP) | From treatment start up to 5 years | Defined as the time (months) from the first dose of study drug until the onset of radiographic disease progression (PD) as assessed by the investigator according to RECIST v1.1. |
| Overall survival (OS) | From treatment start up to 7 years | Defined as the time (months) from the first administration of study drug to death due to any cause. |
Countries
China
Contacts
CONTACTZan Chen
Outcome results
None listed