An Open-label, Randomized, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Trastuzumab Deruxtecan as First-line Treatment of Unresectable, Locally Advanced, or Metastatic NSCLC Harboring HER2 Exon 19 or 20 Mutations.
Primary Objective:
To assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of PFS by BICR in participants with unresectable, locally advanced, or metastatic NSCLC harboring HER2 exon 19 or 20 mutations.
Secondary Objectives:
- To assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of OS.
- To further assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab in terms of PFS by investigator assessment, ORR, DoR, PFS2, and landmark analysis of PFS12 and OS24.
- To assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of CNS-PFS (per RECIST 1.1).
- To assess the safety and tolerability of T-DXd as compared to platinum with pemetrexed plus pembrolizumab.
- To assess the PK of T-DXd, total anti-HER2 antibody and DXd in serum.
- To investigate the immunogenicity of T-DXd.
- To assess the benefit of T-DXd relative to platinum with pemetrexed plus pembrolizumab with patient reported pulmonary symptoms associated with NSCLC.
- To describe patient-reported tolerability of T-DXd as compared to platinum with pemetrexed plus pembrolizumab.
Pembrolizumab(MK-3475)
PEMETREXED
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Missak Haigentz MD
- Principal Investigator
- Rutgers Cancer Institute of New Jersey-University Hospital
Inclusion Criteria
- Participants at least 18 years of age
- Locally advanced and unresectable NSCLC, not amenable to curative therapy, or
metastatic disease
- Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by
tissue NGS or ctDNA
- Treatment-naïve for palliative intent systemic therapy for locally advanced or
metastatic disease
- Left ventricular ejection fraction (LVEF) ≥ 50%
- Measurable disease assessed by Investigator based on RECIST 1.1
- Protocol-defined adequate organ function including cardiac, renal, hepatic function
- ECOG 0-1
- Having tumour tissue available for central testing
Exclusion Criteria
- Tumors with targetable alterations to EGFR (or other targetable mutations including
but not limited to ALK, if routinely tested as a targetable alteration with approved
available therapy)
- Any untreated brain metastases, including asymptomatic or clinically inactive brain
metastases
- Active autoimmune or inflammatory disorders
- Medical history of myocardial infarction within 6 months prior to randomization
- History of non-infectious pneumonitis/ILD, current or suspected ILD
- Lung-specific intercurrent clinical significant severe illness
- Contraindication to platinum-based doublet chemotherapy or pembrolizumab
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.