Neratinib and Fam-Trastuzumab Deruxtecan in Advanced Gastro-esophageal Cancer Patients
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorFox Chase Cancer Center
About this trial
This is Phase 1 dose finding trial with potential dose expansion to evaluate the safety, toxicity, recommended phase 2 dose (RP2D), and maximum tolerated dose (MTD) of Neratinib plus TDxD using a standard 3+3 dose escalation design in patients with metastatic or unresectable gastro-esophageal cancer that are HER2-overexpressing (IHC 3+ or IHC2+/ISH+) and any other gastrointestinal cancer with HER2 expression with IHC3+. Patients must have progressed or been intolerant of at least one prior line of chemotherapy + HER2 directed therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have been diagnosed with histologically or cytologically confirmed gastrointestinal cancer (esophagus, stomach, colon, biliary, pancreas or unknown primary likely GI), and been deemed unresectable or have at least one site of metastatic disease
Patients must have evaluable or measurable disease by RECIST 1.1 criteria
(IHC 3+ or IHC2+/ISH+) advanced gastroesophageal cancer (including gastroesophageal junction adenocarcinoma).
IHC 3+ for other GI cancers
Disqualifiers
Patients who have had chemotherapy, or radiotherapy within 2 weeks prior to C1D1 or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier (secondary hypothyroidism from prior immunotherapy is permissible if controlled on thyroid hormone replacement). Recovery is defined as any treatment onset adverse events returning to baseline or otherwise deemed not clinically significant.
Patients may not be receiving any other investigational agents for advanced cancer and must not have received prior treatment with TDxD
Immunotherapy and treatments involving any investigational agents must be discontinued for >21 days before Cycle 1 Day 1 (C1D1)
Patients with known untreated brain metastases are excluded from this study because of their poor prognosis and frequent development of neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Treated brain metastases are allowed (requires stability on MRI at least 4 weeks after initial treatment). Patients with treated brain metastases are allowed to be treated with steroid and/or anti-convulsants if the dose remains stable or decreases over the last 4 weeks prior to C1D1
Trial design
Design model
Sequential
Treatments tested in this trial
Neratinib Pill
DrugPatients will be enrolled in cohorts of 3 at each dose level of Neratinib (120 mg, 160 mg, 200 mg) daily (days 1 through 21)
Fam-Trastuzumab Deruxtecan-Nxki (TDxD)
Drugstandard dosing of TDxD (5.4mg/m2) on day 1of a 21 day treatment cycle
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: Neratinib plus TDxDExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the combination of TDxD and Neratinib
The rate of dose-limiting toxicities (DLTs) for Neratinib + TDxD during DLT period of 28 days, in patients with advanced gastrointestinal cancer
Time frame
2 yearsSecondary outcomes
1
Determine the Objective Response Rate (ORR) (Complete Response (CR) + Partial Response (PR)) of the combination of TDxD and Neratinib
Rate of grade 3 or higher adverse events with TDxD and Neratinib in patients with advanced gastrointestinal cancer
Time frame
2 years2
Determine the Disease Control Rate (DCR) (CR + PR + Stable Disease (SD)) of the combination of TDxD and Neratinib
Objective Response Rate (ORR) of the combination of TDxD and Neratinib in patients with advanced gastrointestinal cancer (Complete and partial response per RECIST 1.1)
Time frame
2 years3
Determine the Progression Free Survival (PFS) of the combination of TDxD and Neratinib
Progression Free Survival (PFS) of the combination of TDxD and Neratinib in patients with advanced gastrointestinal cancer (time from treatment initiation to disease progression or death from any cause)
Time frame
2 years4
Determine the Overall Survival (OS) of the combination of TDxD and Neratinib
Overall Survival (OS) of the combination of TDxD and Neratinib in patients with advanced gastrointestinal cancer (defined as the time from treatment initiation to death from any cause)
Time frame
2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Fox Chase Cancer Center
Lead sponsor
National Comprehensive Cancer Network
Collaborator
Puma Biotechnology, Inc.
Collaborator
Source ClinicalTrials.gov