A Phase II Platform Trial of Perioperative Therapies in Locally Advanced Unresectable Gastric Cancer (Neo-VIKTORY)
Overview
- Phase
- Phase 2
- Intervention
- Trastuzumab deruxtecan
- Conditions
- Stomach Neoplasms
- Sponsor
- Jeeyun Lee
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Incidence of AEs/SAEs
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
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
Detailed Description
Neoadjuvant therapy will begin following completion of the screening period, and patients will undergo resection surgery 4 to 8 weeks after the last dose of neoadjuvant therapy. Surgery \>8 weeks after the last dose of neoadjuvant therapy may be permitted in consultation with the Sponsor. Adjuvant therapy will begin 4 to 12weeks post-surgery (based on the patient's recovery period). Tumor evaluation using modified RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and ≤28 days after last dose of neoadjuvant therapy and after surgery. Every 12 weeks (±1 week) relative to the Adjuvant Baseline scan for first years and then every 24 weeks (±2 week) until progression/recurrence The imaging modalities used for modified RECIST 1.1 assessment will be CT or MRI scans of chest, abdomen and pelvis. Modified RECIST 1.1 scans will be analyzed by the investigator on site.
Investigators
Jeeyun Lee
Professor
Samsung Medical Center
Eligibility Criteria
Inclusion Criteria
- •1\. Provision of fully informed consent prior to any study specific procedures.
- •2\. Patients must be ≥ 19 years of age
- •3\. Body weight \> 30kg
- •4\. Has a Pathologically documented adenocarcinoma of gastric or gastroesophageal junction with HER2 IHC results.
- •5\. In initial Cohort, HER2 positive (HER2 IHC 3+ or HER2 IHC 2+/ISH positive))
- •6\. Locally advanced unresectable disease by physician's discretion (ex. cT4 or bulky Nx node or localized peritoneal seeding) No evident distant organ metastasis.
- •7\. ECOG performance status PS 0-1 with no deterioration between screening and the first dose of study treatment.
- •8\. Has LVEF ≥ 50% by either echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days before treatment
- •9\. Has measurable target disease assessed by the Investigator based on RECIST version 1.
- •10\. Has adequate organ and bone marrow, liver and renal function within 14 days before treatment (Note: Transfusion (red blood cell or platelet) or G-CSF administration is not allowed within 14 days prior to the day on which bone marrow function is assessed, or at any time after this day and prior to C1D1.)
Exclusion Criteria
- •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.
- •3\. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled hypertension, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent.
- •4\. Unresolved toxicities of ≥ Grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) from prior therapy (excluding vitiligo, alopecia, endocrine disorders that are controlled with replacement hormone therapy, asymptomatic laboratory abnormalities).
- •5\. History of organ transplant.
- •6\. Active primary immunodeficiency/active infectious diseases. Active or prior documented autoimmune or inflammatory disorders (including IBD \[e.g. Crohn's disease, ulcerative colitis or diverticulitis\], SLE, sarcoidosis syndrome, tuberculosis, Wegener syndrome, myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, at screening, that requires use of immunosuppressives, glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis within the past 2 years prior to the start of treatment. The following are exceptions to this criterion:
- •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.
- •HBsAg carrier without active viral infection and under entecavir prophylaxis will be allowed.
- •7\. History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •8\. Active hepatitis B (HBV surface antigen \[HBsAg\] positive) or active hepatitis C. Virus testing is not essential for clinical trial feasibility assessment. Patients who have had or have resolved HBV infection or HCV infection in the past may participate in clinical trials. (Note: For HBsAg-, patient needs to be \>6 months off antiviral treatment.)
Arms & Interventions
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)
Intervention: Trastuzumab deruxtecan
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)
Intervention: Capecitabine
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)
Intervention: Trastuzumab deruxtecan
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)
Intervention: Capecitabine
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)
Intervention: Rilvegostomig
Outcomes
Primary Outcomes
Incidence of AEs/SAEs
Time Frame: Through study completion, an average of 4 years
To evaluate the safety and tolerability (by NCI-CTCAE v5.0)
Secondary Outcomes
- Pathologic CR(Pathological Complete Response)(Through study completion, an average of 1 year)
- EFS (Event-free survival)(Through study completion, an average of 4 years)
- OS (Overall survival)(Through study completion, an average of 4 years)