Perioperative Therapies in Locally Advanced Unresectable Gastric Cancer

Sponsor
Jeeyun Lee
Study ID
NCT06630130
Phase
PHASE2
Status
Recruiting
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Conditions

  • Stomach Neoplasms

Eligibility Criteria

Sex
ALL
Age
19 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • 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)

Study Details

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.

Key Dates

First listed
Oct 8, 2024
Start date
Jan 22, 2025
Status verified
Jun 2026
Primary completion
Oct 30, 2028
Completion
Jun 30, 2029

Study Design

Enrollment
100 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort A : T-DXd and Capecitabine combination
    Neoadjuvant; Trastuzumab Deruxtecan(T-DXd) 5.4mg/kg IV on D1 and Capecitabine 1000mg/m2 PO BID on D1-D14, Q3W for 3 cycles -Adjuvant; Trastuzumab Deruxtecan(T-DXd) 5.4mg/kg IV on D1, Q3W 16 cycles (up to 12 months) and Capecitabine 1000mg/m2 PO BID on D1-D14, Q3W for 4 cycles (up to 3 months)
  • Experimental: Cohort B : T-DXd and Capecitabine and Rilvegostomig combination
    * Neoadjuvant; Trastuzumab Deruxtecan(T-DXd) 5.4mg/kg IV on D1 and Capecitabine 1000mg/m2 PO BID on D1-D14 with Rilvegostomig 750mg IV on D1, Q3W for 3 cycles * Adjuvant; Trastuzumab Deruxtecan(T-DXd) 5.4mg/kg IV with Rilvegostomig 750mg IV on D1, Q3W for 16 cycles (up to 12 months) and Capecitabine 1000mg/m2 PO BID on D1-D14, Q3W for 4 cycles (up to 3 months)
  • Experimental: <Cohort C> Sonesitatug Vedotin(Sone-Ve) + Capecitabine + Durvalumab combination
    * Neoadjuvant; Sonesitatug Vedotin(Sone-Ve) 2.2mg /kg IV with Durvalumab 1500mg IV on D1, and Capecitabine 750mg/m2 PO BID on D1-D14 Q3W for 3 cycles (the order of infusion: Durvalumab -\> Sone-Ve) * Adjuvant; Sonesitatug Vedotin(Sone-Ve) 2.2mg/kgIV with Durvalumab 1500mg IV on D1 and Capecitabine 750mg/m2 PO BID on D1-D14, Q3W for 3 cycles (approximately 2 months) then Sonesitatug Vedotin(Sone-Ve) 2.2mg/kgIV with Durvalumab 1500mg IV on D1 Q3W for 13 cycles (up to 10 months) (the order of infusion: Durvalumab -\> Sone-Ve)
  • Experimental: <Cohort D> Sonesitatug Vedotin(Sone-Ve) + Capecitabine + Oxaliplatin + Durvalumab combination
    * Neoadjuvant; Sonesitatug Vedotin(Sone-Ve) 2.2mg /kg IV with Durvalumab 1500mg IV on D1, and Oxaliplatin 100mg/m2 IV on D1, Capecitabine 750mg/m2 PO BID on D1-D14 Q3W for 3 cycles (the order of infusion: Durvalumab -\> Sone-Ve -\> Oxaliplatin) * Adjuvant; Sonesitatug Vedotin(Sone-Ve) 2.2mg/kgIV with Durvalumab 1500mg IV on D1 and , and Oxaliplatin 100mg/m2 IV on D1, Capecitabine 750mg/m2 PO BID on D1-D14, Q3W for 3 cycles (approximately 2 months) then Sonesitatug Vedotin(Sone-Ve) 2.2mg/kg IV with Durvalumab 1500mg IV on D1 Q3W for 13 cycles (up to 10 months) (the order of infusion: Durvalumab -\> Sone-Ve -\> Oxaliplatin)

Primary Outcome Measure

Incidence of AEs/SAEs [ Time Frame: Through study completion, an average of 4 years ]

Central Contacts

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