Platform Trial Evaluating Treatment of Neoadjuvant Trastuzumab-deruxtecan Containing Combination Therapies for HER2+, Resectable Esophagogastric Adenocarcinoma

NCT06731803 | Active Not Recruiting Phase 1

• 4 other identifiers: NeoART2024-518841-12-00AIO-STO-0124IKF072
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 14

Brief Summary

The study is a phase Ib/II, prospective, single arm, open label, non-randomized, multi-center platform trial assessing the feasibility and safety of different neoadjuvant trastuzumab-deruxtecan containing combinational treatment regimens in patients with HER2 positive, locally advanced, resectable esophagogastric adenocarcinoma

Conditions

Esophagogastric Adenocarcinoma

Keywords

gastric adenocarcinoma; GEJ adenocarcinoma; Her2 positive

Outcome Measures

Primary Outcomes (1)

• Feasibility rate

  Feasibility rate, defined as proportion of patients receiving the protocol treatment according to the planned schedule before surgery without occurrence of at least one dose-limiting toxicity (DLT)

  9 weeks

Secondary Outcomes (2)

• Safety and toxicity

  up to 7.5 months

• Pathological complete remission

  up to 10 weeks

Study Arms (2)

NeoART-001

EXPERIMENTAL

Trastuzumab-deruxtecan 5.4 mg/kg i.v., on day 1, Q3W plus 5-FU/LV: leucovorin 200 mg/m2 i.v., followed by 5-fluorouracil (5-FU) 2600 mg/m2 as a 24-h continuous infusion on day 1, Q2W. Patients will receive three cycles of neoadjuvant T-DXd combined with four cycles 5-FU/LV followed by surgery.

Drug: Trastuzumab deruxtecan + 5FU/LV

NeoART-002

EXPERIMENTAL

Trastuzumab-deruxtecan 5.4 mg/kg i.v., on day 1, Q3W plus FLO: oxaliplatin 85 mg/m2 \& leucovorin 200 mg/m2, each as an i.v. infusion followed by 5-FU 2600 mg/ m2 as a 24-h continuous infusion on day 1, Q2W. Patients will receive three cycles of neoadjuvant T-DXd combined with four cycles 5-FU/LV followed by surgery.

Drug: Trastuzumab deruxtecan + FLO

Interventions

Trastuzumab deruxtecan + FLO DRUG

trastuzumab deruxtecan 5.4 mg/kg i.v., on day 1, Q3W for max 3 cycles plus 4 cycles FLO: oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2, each as an i.v. infusion followed by 5-FU 2600 mg/ m2 as a 24-h continuous infusion on day 1, Q2W for 4 cycles

NeoART-002

Trastuzumab deruxtecan + 5FU/LV DRUG

trastuzumab deruxtecan 5.4 mg/kg i.v., on day 1, Q3W for max 3 cycles plus 4 cycles 5-FU/LV: leucovorin 200 mg/m2 i.v., followed by 5-fluorouracil (5-FU) 2600 mg/m2 as a 24-h continuous infusion on day 1, Q2W for 4 cycles

NeoART-001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient\* has given written informed consent.
• Patient is ≥ 18 years of age at time of signing the written informed consent.
• Patient has histologically proven locally advanced (cT2-4, any cN, M0 OR any cT, cN+, M0 stage) gastric, esophagogastric junction or lower esophageal adenocarcinoma that:
• Is considered technically resectable
• Does not involve distant site of the peritoneal cavity
• confirmed by diagnostic laparoscopy for all patients with tumors located in the stomach and those with type 2 and 3 GEJ adenocarcinomas according to guideline recommendation \[Lordick et al. 2022\].
• Type 1 GEJ and lower esophageal tumors can be enrolled without diagnostic laparoscopy (which is in line with guidelines and the current routine practice in Germany)
• Patient has a HER2 positive tumor (by local testing) defined by HER2 IHC 3+ or IHC 2+ plus ISH positive with a HER2:CEP17 ratio of ≥ 2 according to classically used criteria for defining HER2 positivity \[Lordick et al. 2017\] .
• Patient has a ECOG performance status 0 or 1.
• Patient has adequate blood count, liver-enzymes, and renal function:
• ANC \> 1,500 cells/μL without the use of hematopoietic growth factors
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)\*\*
• Hemoglobin ≥ 9 g/dL\*\*
• Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN

You may not qualify if:

• Patient received previous (radio)chemotherapy or HER2-targeted therapy for the same condition or within the past five years for any other cancerous condition.
• Patient received prior partial or complete esophagogastric tumor resection.
• Patient has known hypersensitivity to any component of the T-DXd formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and/or any known contraindication (including hypersensitivity) to one of the study drugs.
• Patient has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Patient has lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within three months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.).
• Patient received a prior complete pneumonectomy
• Patient has inadequate cardiac function (LVEF value \< 50 %) as determined by echocardiography.
• Patient has a known complete absence of dihydropyrimidine dehydrogenase (DPD) activity
• Patient received treatment with brivudine, sorivudine or their chemically related analogues within 28 days prior to stud enrollment
• Patients has pernicious anemia or other megaloblastic anemia due to vitamin B12 deficiency
• Patient has peripheral sensitive neuropathy with functional deficits.
• Patient has a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation during screening to rule out MI.
• Patient has a corrected QT interval (QTc) prolongation to \> 470 ms (females) or \>450 ms (males) based on average of the screening triplicate12-lead ECG.
• Patient has a history of malignancy other than EGA except for:
• Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study treatment and of low potential risk for recurrence.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Daiichi Sankyo: collaborator

Study Sites (14)

Uniklinikum Salzburg, Universitätsinstitut für Innere Medizin III der PMU

Salzburg, 5020, Austria

Location

Medizinische Universität Wien, Universitätsklinik für Innere Medizin I

Vienna, 1090, Austria

Location

Charite Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

KEM | Kliniken Essen Mitte gGmbH Klinik für Internistische Onkologie / Hämatologie mit Integrierter Palliativmedizin

Essen, 45136, Germany

Location

Krankenhaus Nordwest GmbH Institut für Klinisch-Onkologische Forschung (IKF)

Frankfurt am Main, 60488, Germany

Location

Universitätsmedizin Halle, Universitätsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Hämatologisch-Onkologische Praxis Eppendorf (hope)

Hamburg, 20249, Germany

Location

Nationales Centrum für Tumorerkrankungen

Heidelberg, 69120, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum rechts der Isar München der TU München

München, 81675, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Interventions

trastuzumab deruxtecan

Study Officials

• Salah Al-Batran, Prof. Dr.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All eligible patients in cohort NeoART-001 will receive: Trastuzumab-deruxtecan 5.4 mg/kg i.v., on day 1, Q3W plus 5-FU/LV: leucovorin 200 mg/m2 i.v., followed by 5-fluorouracil (5-FU) 2600 mg/m2 as a 24-h continuous infusion on day 1, Q2W All eligible patients in cohort NeoART-002 will receive: Trastuzumab-deruxtecan 5.4 mg/kg i.v., on day 1, Q3W plus FLO: oxaliplatin 85 mg/m2 \& leucovorin 200 mg/m2, each as an i.v. infusion followed by 5-FU 2600 mg/ m2 as a 24-h continuous infusion on day 1, Q2W followed by surgery determined by the location of the primary tumor and post-operative care according to the guidelines and to local standards outside of this trial.

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 12, 2024
• Study Start: March 25, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (12); AU (2)