A Randomized, Double-Blind, Multicenter, Phase II/III Clinical Study to Evaluate HLX07 (Recombinant Anti-EGFR Humanized Monoclonal Antibody Injection) in Combination With Serplulimab and Chemotherapy Versus Placebo in Combination With Serplulimab or Pembrolizumab and Chemotherapy as First-Line Treatment in Patients With Advanced Squamous Non-Small Cell Lung Cancer (sqNSCLC)
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Shanghai Henlius Biotech
- Enrollment
- 720
- Locations
- 1
- Primary Endpoint
- ORR assessed by BICR (part I)
Overview
Brief Summary
The study consists of two parts:
Part I is a randomized, double-blind, multicenter, parallel-controlled phase II clinical study to evaluate the efficacy and safety of HLX07 in combination with serplulimab and chemotherapy versus placebo in combination with serplulimab and chemotherapy as first-line treatment in patients with sqNSCLC.
Part II is a randomized, double-blind, multicenter, parallel-controlled phase III clinical study to evaluate the efficacy and safety of HLX07 in combination with serplulimab and chemotherapy versus placebo in combination with pembrolizumab and chemotherapy as first-line treatment in patients with sqNSCLC.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The patients voluntarily participate in this clinical study, fully understand and have been informed about the study, have signed the informed consent form (ICF), and are willing to follow and able to complete all study procedures.
- •Male or female, aged 18 years or older at the time of signing the ICF.
- •Histologically confirmed with stage IIIB/IIIC or IV (AJCC 8th edition) squamous NSCLC ineligible for surgery or radical radiotherapy.
- •Patients must provide sufficient tumor tissues that meet the quality requirements for the determination of EGFR and PD-L1 expression levels.
- •Note: Formalin-fixed tumor samples (paraffin blocks or unstained sections, meeting the quality control criteria for testing) collected from lesions that have not received radiotherapy at or after the diagnosis of locally advanced/recurrent or distant metastatic squamous non-small cell lung cancer (sqNSCLC) (from the most recent surgery or biopsy, preferably within half a year prior to randomization) should be provided. Relevant pathology reports must also be provided for the above specimens. For detailed requirements for tissue samples, see the Laboratory Operation Manual.
- •Absence of prior systemic treatment for locally advanced/recurrent or distant metastatic sqNSCLC. Patients who have received prior adjuvant or neoadjuvant therapy are allowed to be enrolled if the adjuvant/neoadjuvant therapy has been completed at least 6 months before the diagnosis of locally advanced/recurrent or distant metastatic sqNSCLC.
- •Prior non-systemic anti-tumor therapy or Chinese herbal anti-tumor therapy must have ended for ≥ 2 weeks before randomization, and treatment-related AEs have resolved to Grade ≤ 1 according to Common Terminology Criteria for Adverse Events (CTCAE) 6.0 (except for Grade 2 alopecia).
- •At least one measurable target lesion assessed by BICR as per RECIST v1.1 within 4 weeks before randomization.
- •Note: Measurable target lesions cannot be selected from prior radiotherapy sites. A lesion at the prior radiotherapy site may be selected as the target lesion if it is the only available lesion, and should provide the imaging data of the lesion before and after an unequivocal progression after the radiotherapy.
- •An ECOG performance status score of 0 or 1 within 7 days prior to randomization.
Exclusion Criteria
- •Histologically confirmed non-sqNSCLC. Mixed tumors will be classified by the predominant cell type. Patients with small cell component or neuroendocrine carcinoma component are not eligible. For the non-small cell histology, patients with squamous component that is predominant (e.g., adenosquamous) are eligible.
- •Known EGFR-sensitizing mutation, ALK/ROS1 gene rearrangement, or other actionable driver oncogenes for which there are locally approved targeted first-line therapies.
- •Note: If the EGFR, ALK, ROS1 and other actionable driver oncogenes statuses are unknown, testing is not mandatory, unless there are high-risk factors (such as non-smoking female patients), under which circumstances testing of EGFR and other mutations may be considered.
- •Other malignancies within 5 years or active. Patients with localized tumors that have been cured, such as basal cell carcinoma, squamous-cell skin cancer, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, and breast cancer in situ, are eligible.
- •Scheduled or previous organ or bone marrow transplantation.
- •Uncontrollable pleural effusion, pericardial effusion, or ascites.
- •Active central nervous system (CNS) metastases and/or carcinomatous meningitis known or diagnosed at screening. However, the following patients may be enrolled:
- •Patients with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain metastases, no requirement for glucocorticoid therapy, and lesion size ≤ 1.5 cm) may be enrolled, but are required to receive regular brain imaging as a site of lesion.
- •Patients with treated brain metastases that have been stable for at least 1 month, with no evidence of new or enlarging brain metastases, and with glucocorticoid discontinued ≥ 3 days prior to randomization.
- •Stable brain metastases should be confirmed before randomization.
Arms & Interventions
Part I (phase 2)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: HLX07 (Drug)
Part I (phase 2)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Serplulimab (Drug)
Part I (phase 2)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Carboplatin (Drug)
Part I (phase 2)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Paclitaxel or Nab-Paclitaxel (Drug)
Part I (phase 2)-Group B
Placebo + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: HLX07 placebo (Drug)
Part I (phase 2)-Group B
Placebo + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Serplulimab (Drug)
Part I (phase 2)-Group B
Placebo + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Carboplatin (Drug)
Part I (phase 2)-Group B
Placebo + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Paclitaxel or Nab-Paclitaxel (Drug)
Part II (phase 3)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: HLX07 (Drug)
Part II (phase 3)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Serplulimab (Drug)
Part II (phase 3)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Carboplatin (Drug)
Part II (phase 3)-Group A
HLX07 + serplulimab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with HLX07 in combination with serplulimab, with serplulimab administered for up to 2 years.
Intervention: Paclitaxel or Nab-Paclitaxel (Drug)
Part II (phase 3)-Group B
Placebo + pembrolizumab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with pembrolizumab, with pembrolizumab administered for up to 2 years.
Intervention: HLX07 placebo (Drug)
Part II (phase 3)-Group B
Placebo + pembrolizumab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with pembrolizumab, with pembrolizumab administered for up to 2 years.
Intervention: Pembrolizumab (Drug)
Part II (phase 3)-Group B
Placebo + pembrolizumab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with pembrolizumab, with pembrolizumab administered for up to 2 years.
Intervention: Carboplatin (Drug)
Part II (phase 3)-Group B
Placebo + pembrolizumab + carboplatin + paclitaxel or nab-paclitaxel, once every 3 weeks for a total of 4 cycles, followed by maintenance therapy with placebo in combination with pembrolizumab, with pembrolizumab administered for up to 2 years.
Intervention: Paclitaxel or Nab-Paclitaxel (Drug)
Outcomes
Primary Outcomes
ORR assessed by BICR (part I)
Time Frame: Assessed up to appoximately 6 months from enrollment
Defined as the proportion of participants who achieve a best overall response of CR or PR
PFS assessed by BICR (part II)
Time Frame: Assessed up to appoximately 23 months from enrollment
Defined as the time from randomization to the first documentation of PD (RECIST v1.1) or death due to any cause (whichever occurs first)
OS (part II)
Time Frame: Assessed up to appoximately 42 months from enrollment
Defined as the time from randomization to death due to any cause
PFS assessed by BICR (part I)
Time Frame: Assessed up to appoximately 16 months from enrollment
Defined as the time from randomization to the first documentation of PD (RECIST v1.1) or death due to any cause (whichever occurs first)
Secondary Outcomes
- Incidence of adverse events (part I)(Assessed up to appoximately 35 months from enrollment)
- PFS assessed by investigator (part II)(Assessed up to appoximately 23 months from enrollment)
- DCR (part I)(Assessed up to appoximately 6 months from enrollment)
- OS (part I)(Assessed up to appoximately 35 months from enrollment)
- DOR (part I)(Assessed up to appoximately 35 months from enrollment)
- ORR assessed by investigator (part I)(Assessed up to appoximately 6 months from enrollment)
- PFS assessed by investigator (part I)(Assessed up to appoximately 16 months from enrollment)
- DCR (part II)(Assessed up to appoximately 6 months from enrollment)
- DOR (part II)(Assessed up to appoximately 42 months from enrollment)
- ORR (part II)(Assessed up to appoximately 6 months from enrollment)
- Incidence of adverse events (part II)(Assessed up to appoximately 42 months from enrollment)