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Perioperative Therapies in Locally Advanced Unresectable Gastric Cancer

ConditionStomach Neoplasms
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age19+
SponsorJeeyun Lee

About this trial

Gastric cancer (GC) is the fifth most commonly diagnosed cancer, with over one million cases diagnosed annually worldwide. Human epidermal growth factor receptor 2 (HER2) overexpression in GC (seen in 4.4% to 53.4% of patients in different reports) is predictive biomarker of response to HER2-targeting therapies.

Trastuzumab in combination with cisplatin or oxaliplatin, and a fluoropyrimidine (capecitabine or 5-fluorouracil \[5-FU\]), is approved anti-HER2 therapy for first-line treatment of HER2-positive gastric or gastroesophageal junction (GEJ) cancer.

Rilvegostomig 750 mg Q3W was selected as recommended Phase 2 dose based on all available ARTEMIDE-01 clinical safety, efficacy, PK, RO data as well as modeling analysis. The dose of 750 mg Q3W is predicted to achieve intra-tumoral RO of ≥ 90% in the majority of participants across a broad spectrum of conditions.

This is a phase II study to initially assess the efficacy of perioperative Trastuzumab Deruxtecan (T-DXd) and Capecitabine combination with or without Rilvegostomig in patients with HER2 positive locally advanced unresectable GC and potentially by subsequent protocol amendment in HER2 low locally advanced GC. Other agents may also subsequently be assessed in this protocol, by protocol amendments .

\---------------------------------------------------------------------------------------------------- Therefore, these studies provide robust evidence that immune checkpoint inhibitors plus chemotherapy, specifically the perioperative durvalumab plus FLOT regimen, can increase pCR rate and significantly improve long-term survival outcomes for patients with resectable gastric, GEJ, or esophageal cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Provision of fully informed consent prior to any study specific procedures.

Patients must be ≥ 19 years of age

Have a life expectancy of at least 12 weeks

Body weight > 30kg( > 35kg for Rilvegostomig)

Disqualifiers

1. Patients with evident peritoneal metastasis (including tumor cells in peritoneal fluid) or distant metastasis 2. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency based on either local or central laboratory testing. Central laboratory testing will be available for patients where testing is SOC and with unknown DPD status.

Subjects with vitiligo or alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment; patients with coeliac disease controlled by diet alone and patients without active disease in the last 5 years may be included after consultation with Chief Investigator.

Absence of HCV co-infection or history of HCV co-infection.

Access to a local Hepatitis B expert during and after the study. Such participants should be closely monitored for HBV reactivation. . Consideration should be given to exclusion of all participants with HBV infection if comparator or combination study treatments are associated with a high risk of HBV infection reactivation are incompatible with anti-viral medications.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Trastuzumab deruxtecan

    Drug

    * Neoadjuvant; Trastuzumab Deruxtecan(T-DXd) 5.4mg/kg IV on D1, Q3W for 3 cycles * Adjuvant; Trastuzumab Deruxtecan(T-DXd) 5.4mg/kg IV on D1, Q3W 16 cycles (up to 12 months)

  • Capecitabine

    Drug

    * Neoadjuvant; Capecitabine 1000mg/m2 PO BID on D1-D14, Q3W for 3 cycles * Adjuvant; Capecitabine 1000mg/m2 PO BID on D1-D14, Q3W for 4 cycles (up to 3 months)

  • Rilvegostomig

    Drug

    (Only Cohort B) * Neoadjuvant; Rilvegostomig 750mg IV on D1, Q3W for 3 cycles * Adjuvant; Rilvegostomig 750mg IV on D1, Q3W for 16 cycles (up to 12 months)

  • Durvalumab

    Drug

    * Neoadjuvant; Durvalumab 1500mg IV on D1, Q3W for 3 cycles * Adjuvant; Durvalumab 1500mg IV on D1 Q3W for 16 cycles (up to 12 months)

  • Sonesitatug Vedotin

    Drug

    * Neoadjuvant; Sonesitatug Vedotin(Sone-Ve) 2.2mg /kg IV on D1, Q3W for 3 cycles * Adjuvant; Sonesitatug Vedotin(Sone-Ve) 2.2mg/kg IV on D1 Q3W for 16 cycles (up to 12 months)

  • Oxaliplatin

    Drug

    Neoadjuvant; Oxaliplatin 100mg/m2 IV on D1, Q3W for 3 cycles -Adjuvant; Oxaliplatin 100mg/m2 IV on D1, Q3W for 3 cycles (approximately 2 months)

Treatment groups

100 Participants
are divided into 4 treatment groups
Group A: Cohort A : T-DXd and Capecitabine combinationExperimental treatment 2 interventions
Group B: Cohort B : T-DXd and Capecitabine and Rilvegostomig combinationExperimental treatment 3 interventions
Group C: <Cohort C> Sonesitatug Vedotin(Sone-Ve) + Capecitabine + Durvalumab combinationExperimental treatment 3 interventions
Group D: <Cohort D> Sonesitatug Vedotin(Sone-Ve) + Capecitabine + Oxaliplatin + Durvalumab combinationExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Incidence of AEs/SAEs

To evaluate the safety and tolerability (by NCI-CTCAE v5.0)

Time frame
Through study completion, an average of 4 years

Secondary outcomes

1

Pathologic CR(Pathological Complete Response)

To assess by OP pathology review

Time frame
Through study completion, an average of 1 year
2

EFS (Event-free survival)

Modified Recist v1.1

Time frame
Through study completion, an average of 4 years
3

OS (Overall survival)

Kaplan-Meier method

Time frame
Through study completion, an average of 4 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Jeeyun Lee

Lead sponsor

Samsung Medical Center

Sponsor institution

Source ClinicalTrials.gov
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