Phase II Study of Avelumab plus chemotherapy for patients with resectable Gastric cancer (GC) or Gastroesophageal Junction cancer (GEJC). Moneo trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vall D Hebron Institute Of Oncology

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Oct 2024 → ongoing

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MERCK, S.L.U.

External identifiers

EU CT number

2024-516777-77-00

EudraCT number

2019-000782-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective is to investigate whether the addition of avelumab to the neoadjuvant chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) improves efficacy in terms of pathological complete response (pCR) rate, in GC and GEJC patients, compared with the historical controls where neoadjuvant chemotherapy alone was administrated.

Secondary objectives 3

1. To evaluate the addition of avelumab to the perioperative chemotherapy in regard to the following: o Overall survival (OS) o Disease-free survival (DFS) o Progression-free survival (PFS) o Surgical complete resection rate (R0) o Overall response rate (ORR)
2. To determine the safety and tolerability of avelumab with FLOT chemotherapy.
3. To perform a comprehensive analysis of biomarkers (exploratory endpoints)

Conditions and MedDRA coding

Resectable Gastric cancer (GC) or Gastroesophageal Junction cancer (GEJC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically proven, gastric or GEJ adenocarcinoma (Siewert I-III).
2. Availability of two paraffin blocks from the diagnostic endoscopic biopsy (and a fresh biopsy if possible), and another tumor block (paraffin) from the surgical specimen. In some sites, a fresh tumor sample will be required.
3. Have evaluable disease as defined by RECIST 1.1 and determined by investigator assessment, with the absence of distant metastases on CT scan of thorax, abdomen and pelvis.
4. Patient medically fit and amenable to gastrectomy/esophagectomy with curative intent as confirmed by a multidisciplinary team discussion.
5. UICC tumor stage Ib (T1N1 only, T2N0 not eligible) to IIIC, as defined by CT, according to the 7th AJCC Edition.
6. Age ≥ 18 years.
7. WHO performance status 0-1.
8. Adequate organ function (assessed within 7 calendar days prior treatment initiation): a. White blood cell count (WBC) ≥ 3 x 109 /L b. Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L c. Platelets ≥ 100 x 109 /L d. Estimated glomerular filtration rate should be ≥ 50 ml/min e. Total bilirubin within normal limits (if the patient has documented Gilbert’s disease ≤ 1.5 x ULN or direct bilirubin ≤ ULN). f. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN.
9. In case of anticoagulation, investigator and patient should agree to replace any oral anticoagulation by subcutaneous administration of low-molecular weight heparin in equivalent doses before treatment start;
10. For women who are not postmenopausal (> 12 months of non-therapy induced amenorrhea) single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last treatment dose
11. For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last dose of study treatment. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods for contraception.
12. For all female patients who are not confirmed postmenopausal (> 12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus) a negative serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) result should be available before treatment and within 7 days from treatment start should be performed. Female patients should not be breast feeding.
13. Written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion criteria 18

1. Other histology different from adenocarcinoma.
2. s had previous therapy for gastric or GEJ cancer.
3. Known hypersensitivity to the components of anti-PD-L1, docetaxel, oxaliplatin, fluorouracil/leucovorin.
4. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
5. Previous malignancy within the last 5 years, except for adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer, or other curatively treated cancer without impact on the patient’s overall prognosis according to the judgment of the investigator.
6. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those condition should be discussed with the patient before registration in the trial.
7. tory of clinically significant comorbidities.
8. Patients medically unfit for FLOT chemotherapy, according to the local guidance.
9. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
10. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). History or evidence of interstitial lung disease or active, non-infectious pneumonitis.
11. Active infection requiring systemic therapy.
12. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Test for HBV and HCV are required for the screening.
13. Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu-vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.
14. Prior organ transplantation including allogenic stem-cell transplantation.
15. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI-CTCAE v4.0 Grade ≥ 3).
16. Persisting toxicity related to prior therapy (NCI-CTCAE v4.0 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator’s judgment are acceptable.
17. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
18. Pregnant women and lactating females are excluded from this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathological complete response (pCR) rate, where pCR is defined as the absence of residual tumor based on evaluation of the resected esophagogastric specimen according to Becker remission criteria [1].

Secondary endpoints 6

1. Overall survival (OS) [time frame: from the initial date of neoadjuvant chemotherapy to the date of death due to any cause. Patients without documentation of death at the time of analysis will be censored at the last follow-up date]. Estimated using Kaplan-Meier method.
2. Disease-free survival (DFS) [time frame: from the surgery to the first observation of disease relapse or death due to any cause. Patients without an event prior to the time of analysis will be censored at the last relapse-free assessment]. Relapse is defined according to RECIST v1.1. Estimated using Kaplan- Meier method.
3. Progression-free survival (PFS) [time frame: from the initial date of neoadjuvant chemotherapy to the date of first documentation of disease progression or death due to any cause, whichever occurs first. Patients without an event prior to the time of analysis will be censored at the last assessment that is stable disease (SD) or better]. Progression is defined according to RECIST v1.1. Estimated using Kaplan-Meier method.
4. Surgical complete resection rate (R0). This is a complete macroscopic resection of the gross tumor with negative surgical margins
5. Overall Response rate (ORR) to neoadjuvancy, as the proportion of subjects with complete response (CR)and partial response (PR), according to RECIST v1.1. [time frame: from the initial date of neoadjuvant chemotherapy to 3 years post- treatment).
6. Safety endpoints: safety of the combination of avelumab with FLOT chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) Exploratory Endpoints • Pathological immune response (pIR) • Characterization of the immune contexture • Immunodynamic follow-up • TCR clonality assessment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vall D Hebron Institute Of Oncology

Sponsor organisation

Vall D Hebron Institute Of Oncology

Address

Calle Natzaret 115

City

Barcelona

Postcode

08035

Country

Spain

Scientific contact point

Organisation

Vall D Hebron Institute Of Oncology

Contact name

Coordinator investigator

Public contact point

Organisation

Vall D Hebron Institute Of Oncology

Contact name

CRO

Third parties 1

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications