A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma

Browse trials for

• Stomach Neoplasms 2,842

Keywords

• Locally Advanced Resectable Gastroesophageal Adenocarcinoma
• Gastroesophageal Junction
• Neoadjuvant Treatment
• Perioperative Treatment
• Gastric cancer
• Immune checkpoint inhibitors
• Chemotherapy

Study arms

• Experimental
  Sub-study 1: Cohort 1a - Sonesitatug Vedotin plus Rilvegostomig and 5-FU or Capecitabine

  Participants will receive Sonesitatug Vedotin (Dose A) plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose A) plus Rilvegostomig as adjuvant therapy 2.

  Drug: Sonesitatug Vedotin · Drug: Rilvegostomig · Drug: Capecitabine · Drug: 5-Fluorouracil (5-FU)

• Experimental
  Sub-study 2: T-DXd plus Rilvegostomig and 5-FU or Capecitabine

  Participants will receive T-DXd plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.

  Drug: Rilvegostomig · Drug: Trastuzumab Deruxtecan (T-DXd) · Drug: Capecitabine · Drug: 5-Fluorouracil (5-FU)

• Experimental
  Sub-study 3: Rilvegostomig plus FLOT chemotherapy

  Participants will receive Rilvegostomig plus FLOT chemotherapy as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.

  Drug: Rilvegostomig · Drug: FLOT Chemotherapy

• Experimental
  Sub-study 1: Cohort 1b - Sonesitatug Vedotin plus Rilvegostomig and Capecitabine

  Participants will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig and Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig as adjuvant therapy 2.

  Drug: Sonesitatug Vedotin · Drug: Rilvegostomig · Drug: Capecitabine

• Experimental
  Sub-study 1: Cohort 1c - Sonesitatug Vedotin plus Rilvegostomig plus 5-FU and calcium folinate

  Participants will receive Sonesitatug Vedotin (Dose C) plus Rilvegostomig plus 5-FU and calcium folinate as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose C) plus Rilvegostomig as adjuvant therapy 2.

  Drug: Sonesitatug Vedotin · Drug: Rilvegostomig · Drug: 5-Fluorouracil (5-FU) · Drug: Calcium folinate

Interventions

• DrugSonesitatug Vedotin

  Sonesitatug Vedotin will be administered as an IV infusion.

  Also known as: AZD0901

• DrugRilvegostomig

  Rilvegostomig will be administered as an IV infusion.

  Also known as: AZD2936

• DrugTrastuzumab Deruxtecan (T-DXd)

  T-DXd will be administered as an IV infusion.

  Also known as: DS-8201a

• DrugCapecitabine

  Capecitabine (Fluoropyrimidine) will be administered orally as chemotherapy standard of care.

• Drug5-Fluorouracil (5-FU)

  5-FU (Fluoropyrimidine) will be administered as a continuous IV infusion as chemotherapy standard of care.

• DrugFLOT Chemotherapy

  FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel) Chemotherapy will be administered as an IV infusion.

• DrugCalcium folinate

  Calcium folinate will be administered as an IV infusion as chemotherapy standard of care.

  Also known as: Leucovorin

Primary outcomes

1. Number of participants with adverse events (AEs) and serious adverse events (SAEs)

   To assess the safety and tolerability of perioperative treatment.

   Time frame: Until sub-study completion, up to 38 months

2. Percentage of participants with pathological complete response (pCR)

   pCR is defined as no viable cancer cells, including lymph nodes after complete evaluation in the resected gastric, GEJ, or esophageal cancer specimen and all sampled regional lymph nodes following neoadjuvant treatment.

   Time frame: Until sub-study completion, up to 38 months

Secondary outcomes

1. Surgery completion rate

   Surgery completion rate is defined as the percentage of participants who received gastrectomy or gastroesophagectomy or esophagectomy.

   Time frame: Until sub-study completion, up to 38 months

2. R0 resection (complete resection) rate

   R0 resection (complete resection) rate is the percentage of participants who received gastrectomy or gastroesophagectomy or esophagectomy and had a confirmed margin-negative resection.

   Time frame: Until sub-study completion, up to 38 months

3. Percentage of participants with tumor downstaging

   Tumor downstaging is defined as the lowering of the primary tumor (T) and/or regional lymph nodes (N) from pre-neoadjuvant clinical staging (pre-cTN) to post-neoadjuvant clinical staging (post-cTN) and to postoperative pathological staging (ypTN).

   Time frame: Until sub-study completion, up to 38 months

4. Event-free survival (EFS)

   EFS is defined as the time from the first dose of study intervention to documented Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or non-RECIST 1.1 disease progression that precludes radical surgery or requires non-protocol therapy during the neoadjuvant through surgery period, or to documented RECIST 1.1 or biopsy-confirmed non-RECIST 1.1 recurrence or progression of disease during the adjuvant period, or death due to any cause at any time.

   Time frame: Until sub-study completion, up to 38 months

5. Disease-free survival (DFS)

   DFS is defined as the time elapsed from the date of the first post-surgery scan (ie, Adjuvant Baseline scan) until the date of first evidence of disease recurrence as determined by Investigator using RECIST 1.1 assessment (local or distant), or death due to any cause, whichever occurs first.

   Time frame: Until sub-study completion, up to 38 months

6. Objective response rate (ORR)

   ORR is defined as the percentage of participants who have a CR or PR as determined by Investigator using RECIST 1.1 at their latest assessment prior to surgery.

   Time frame: Until sub-study completion, up to 38 months

7. Overall survival (OS)

   OS is defined as the time from the first dose of the study intervention until the date of death due to any cause regardless of whether participant withdraws from treatment or receives another anti-cancer therapy.

   Time frame: Until sub-study completion, up to 38 months

8. Serum concentrations of study interventions

   To assess the serum concentrations of study interventions in participants receiving perioperative treatment.

   Time frame: Until sub-study completion, up to 38 months

9. Number of participants with positive anti-drug antibodies (ADA)

   To assess the immunogenicity of study interventions in participants receiving perioperative treatment.

   Time frame: Until sub-study completion, up to 38 months

Individual participant data

Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting information: Study protocol, Sap