A Phase 2 Clinical Study of Combination Therapy With ABSK043 and Firmonertinib

A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of ABSK043 Combined With Firmonertinib in Patients With EGFR Mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer(NSCLC)

This is an open-label phase 2 study to evaluate the safety, tolerability and preliminary anti-tumour activity of ABSK043 in combination with Firmonertinib in patients with Epidermal Growth Factor Receptor-mutated (EGFRm+) locally advanced or metastatic NSCLC.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer With EGFR Mutation
• Intervention / Treatment: Drug: ABSK043 in combination with Firmonertinib

Detailed Description

This is a Phase II, open-label, multicentre study of ABSK043 administered orally in combination with Firmonertinib to patients with EGFRm+ advanced NSCLC. The study has been designed to allow an investigation of the optimal combination dose and schedule whilst ensuring the safety of patients with intensive safety monitoring. There are two main parts to this study; Part A, dose escalation and Parts B Dose expansion. The expansion part will evaluate the efficacy of ABSK043 in combination with Firmonertinib as first-line treatment for locally advanced or metastatic NSCLC patients with EGFR-mutated at the one or more recommended dose.

Dose escalation:

• Post-line: Patients with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with systemic treatment

Dose Expansion:

• First-Line: Patients with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation, and without prior systemic therapy for advanced or metastatic disease.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: YUAN LU; Phone Number: +86-21-68910052; Email: clinical@abbisko.cn
• Study Contact Backup: Name: Yinan Lin; Phone Number: +86-21-68910052; Email: yinan.lin@abbisko.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • Hanhui Cancer Hospital
      • Principal Investigator: Yueyin Pan
      • Contact: Yueyin Pan
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: yan Yu
      • Principal Investigator: Yan Yu
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital Tongji Medical College Huzhong University of Science and Techology
      • Contact: Xiaorong Dong
      • Principal Investigator: Xiaorong Dong
  • Jilin
    • Changchun, Jilin, China
      • Not yet recruiting
      • Jilin Cancer Hospital
      • Principal Investigator: Ying Cheng
      • Contact: Ying Cheng
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Chest Hospital
      • Principal Investigator: Shun Lu
      • Contact: Shun Lu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically documented locally advanced or metastatic NSCLC
2. At least 1 measurable lesion as assessed by Investigator as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
3. Inclusion Criteria Specific to Dose Escalation cohort and Dose Confirmation Cohort：Must has disease progression following treatment with EGFR-TKI in the locally advanced or metastatic setting for locally advanced or metastatic disease Documentation of PDL1 expression positive (TPS/TC≥1%)detected from tumor tissue Inclusion Criteria Specific to Dose expansion Cohort： Must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting PDL1 expression positive (TPS/TC≥1%) as assessed by central laboratory from tumor tissue
4. Adequate bone marrow reserve and organ function based on local laboratory data .
5. Documented genetic testing reports confirmed the presence of EGFR L858R or EGFR exon 19 del mutations in tumor or plasma ctDNA.

Exclusion Criteria:

1. 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. Has spinal cord compression or clinically active central nervous system metastases, defined as symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study
4. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, Grade ≤1 or baseline.
5. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy.
6. Uncontrolled or significant cardiovascular disease
7. Has a known human immunodeficiency virus (HIV) infection that is not well controlled.
8. Any evidence of severe or uncontrolled diseases or other factors which in the Investigator's opinion makes it undesirable for the patients to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ABSK043 in combination with Firmonertinib; This is an open-label phase 2 study with an escalation part and an expansion part.; Escalation part: Previously treated patients with EGFR Mutated NSCLC will be enrolled.Dose escalation cohort: up to 12 patients;Dose confirmation cohort: at least 3 patients, and up to 12 patients.; Expansion part:Dose expansion cohort: up to 30 treatment-naïve patients with EGFR Mutated NSCLC are expected to be enrolled.

Drug: ABSK043 in combination with Firmonertinib; Two potential dose levels ：400 mg twice daily （BID） and 800 mg BID) of ABSK043 are prespecified and firmonertinib will be administered orally at a fixed dose of 80 mg once daily (QD). Patients in dose escalation cohort will receive the ABSK043, 400 mg BID and firmonertinib 80 mg QD as the starting dose for the combination therapy. 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. After Cycle 1, patients will continue to receive combination therapy every 21 days until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator decision to discontinue treatment, or end of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLT	Dose-limiting toxicities	At the end of Cycle 1 (each cycle is 21 days)
AEs	Adverse events	From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of furmonertinib mesylate, whichever occurs first, up to 30 months.
SAEs	Serious adverse events (SAEs)	From the time patients sign the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of furmonertinib mesylate, whichever occurs first, up to 30 months.
AESIs	Adverse events of special interest (AESIs)	From the time patients sign the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of furmonertinib mesylate, whichever occurs first, up to 30 months.
PFS rate at 12 month	Progression-free survival at 12 month	From the time patients receive the first dose of study drug to 12 months，assessed up to 30 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	Disease control rate	From date of enrollment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator decision to discontinue treatment, or end of the study, whichever comes first，assessed up to 30 months.
Cmax	Maximum observed concentration	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
AUC	area under the concentration-time curve area under the concentration-time curve area under the concentration-time curve	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
t1/2	elimination half-life	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
Vz/F	apparent volume of distribution	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
CL/F	apparent oral clearance	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
Cmax,ss	maximum observed concentration after multiple doses	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
Cmin,ss	minimum observed concentration after multiple doses	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
AUCtau,ss	area under the concentration-time curve after multiple doses	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
AR	accumulation ratio	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
tmax	time to maximum observed concentration	From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.
ORR	Objective response rate	From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
DOR	Duration of response	From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
PFS	Progression-free survival	From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
OS	Overall survival	From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 30 months.
TTP	Time to progression	From date of enrolment #Cycle1 Day1# until disease progression, assessed up to 30 months.

Collaborators and Investigators

• Sponsor: Abbisko Therapeutics Co, Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): October 31, 2024

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ABSK043-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No