SYS6090 Combination Therapy in Advanced Lung Cancer

Official title

A Phase Ib/II Study to Evaluate the Safety, Tolerability, and Efficacy of SYS6090 in Combination With Other Therapies in Participants With Advanced Lung Cancer

Overview

This is an open-label, multi-cohort, multicenter Phase Ib/II clinical study designed to evaluate the safety, tolerability, and efficacy of SYS6090 injection in combination with chemotherapy or chemotherapy and bevacizumab or SYS6010 (an EGFR ADC) in participants with advanced lung cancer.

Interventions

• Drug SYS6090 + pemetrexed + platinum-based chemotherapy
  In this group, participants will receive SYS6090 in combination with pemetrexed and platinum-based chemotherapy.
• Drug SYS6090 + paclitaxel + platinum-based chemotherapy
  In this group, participants will receive SYS6090 in combination with paclitaxel and platinum-based chemotherapy.
• Drug SYS6090 + docetaxel
  In this group, participants will receive SYS6090 in combination with docetaxel.
• Drug SYS6090 + pemetrexed + bevacizumab + platinum-based chemotherapy
  In this group, participants will receive SYS6090 in combination with pemetrexed, bevacizumab, and platinum-based chemotherapy
• Drug SYS6090 + SYS6010
  In this group, participants will receive SYS6090 and SYS6010.
• Drug SYS6090 + etoposide + platinum-based chemotherapy
  In this group, participants will receive SYS6090 in combination with etoposide and platinum-based chemotherapy.
• Drug SYS6090 + chemotherapy or other anticancer therapy
  In this group, participants will receive SYS6090 in combination with chemotherapy or other anticancer therapies.

Primary outcome measures

• Dose-Limiting Toxicity (DLT) (Phase Ib) [Time frame: Approximately 21 days.]
• Adverse Events (AEs) (Phase Ib) [Time frame: Up to 90 days after the last administration]
• Objective response rate (ORR) (Phase II) [Time frame: Through out the study (up to 2 years)]

Secondary outcome measures (6)

• Cmax of SYS6090 (and SYS6010 if applicable) [Time frame: Through out the study (up to 2 years)]
• AUC0-t of SYS6090 (and SYS6010 if applicable) [Time frame: Through out the study (up to 2 years)]
• Clearance (CL) of SYS6090 (and SYS6010 if applicable) [Time frame: Through out the study (up to 2 years)]
• Other Efficacy Endpoints Assessed by RECIST v1.1 (DoR, DCR, TTR, PFS, and OS) [Time frame: Through out the study (up to 2 years)]
• Adverse Events (AEs) (Phase II) [Time frame: Through out the study (up to 2 years)]
• Correlation between Biomarker Levels and Preliminary Efficacy [Time frame: Through out the study (up to 2 years)]

Eligibility criteria

Inclusion criteria

• Voluntarily signed written informed consent.
• Age 18 to 75 years at the time of informed consent, with no restriction on sex.
• Histologically or cytologically confirmed unresectable locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-small cell lung cancer (NSCLC) according to the AJCC/UICC Cancer Staging System, 8th edition, or extensive-stage small cell lung cancer (SCLC), not amenable to curative surgical resection or definitive chemoradiotherapy.
• At least one measurable lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Estimated life expectancy of at least 3 months.
• Has protocol-defined adequate organ and bone marrow function.

Exclusion criteria

• Use of systemic corticosteroids or other immunosuppressive therapies within 14 days prior to the first dose of study treatment, except for physiologic replacement doses or permitted local, inhaled, or prophylactic use.
• Unresolved > Grade 1 toxicities related to prior anticancer therapy (except for toxicities judged by the investigator to pose no safety risk).
• For Cohorts 5A and 5B: prior permanent discontinuation of EGFR-targeted therapy due to dermatologic toxicity, or presence of dermatologic diseases requiring systemic treatment.
• Known active central nervous system metastases or leptomeningeal metastases, except for stable and adequately treated brain metastases without the need for ongoing corticosteroids or antiepileptic therapy.
• History of interstitial lung disease or non-infectious pneumonitis requiring corticosteroid treatment; current ILD or non-infectious pneumonitis; or inability to exclude these conditions at screening.
• History of severe cardiovascular or cerebrovascular disease.
• Active or recurrent autoimmune disease requiring systemic treatment, except for clinically stable or well-controlled conditions as specified in the protocol.
• Prior immunotherapy associated with severe immune-related adverse events (≥ Grade 3) or immune-related myocarditis (≥ Grade 2), excluding stable immune-related endocrine disorders.
• Clinically significant bleeding events (≥ Grade 2 according to NCI-CTCAE v6.0) within 4 weeks prior to the first dose of study treatment.
• Arterial or venous thromboembolic events within 6 months prior to the first dose of study treatment, unless judged by the investigator to be clinically stable and low risk.
• Presence of ascites or pleural effusion requiring drainage within 14 days prior to the first dose.
• Known hypersensitivity to any component of the study treatment, history of severe hypersensitivity or infusion-related reactions to protein-based therapies, or poorly controlled asthma.
• Untreated spinal cord compression.
• History of other malignancies within 2 years prior to enrollment or concurrent active malignancy, except for cured localized tumors. -

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07472647 · SYS6090-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗