Tornado : Randomized Phase Ii Study of Neoadjuvant Chemotherapy Plus Retifanlimab (INCMGA00012) in Patients with Selected Retroperitoneal Sarcomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Bergonie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Mar 2022 → ongoing

Decision date (initial)

2024-09-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509498-21-00

EudraCT number

2021-001085-37

ClinicalTrials.gov

NCT04968106

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacogenomic, Therapy, Safety

To investigate the antitumor activity of retifanlimab (INCMGA00012) when prescribed in association with neoadjuvant chemotherapy (Doxorubicin + Ifosfamide) in patients with selected sarcomas. Primary efficacy endpoint is histological response based on surgical sample.

Secondary objectives 2

1. To investigate the antitumor activity of retifanlimab when prescribed in association with neoadjuvant chemotherapy (Doxorubicin + Ifosfamide) in terms of additional efficacy endpoints: progression-free (PFS) and overall survival (OS), assessed at one and three years.
2. To evaluate the safety profile of retifanlimab when prescribed in association with neoadjuvant chemotherapy (Doxorubicin + Ifosfamide) (NCI-CTCAE v5).

Conditions and MedDRA coding

Adult patients with treatment-naïve surgically non-metastatic and resectable primary retroperitoneal, limbs and trunk wall undifferentiated pleomorphic sarcomas.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Patients with grade 2 or grade 3 undifferentiated pleomorphic sarcoma (limb, trunk wall, retroperitoneum) histologically confirmed and reviewed by the RRePS Network (Réseau de Référence en Pathologie des Viscères et des tissus mous) as recommended by the French National Cancer Institute(Inca),
2. Deleted MSA4.
3. Deleted MSA4.
4. Non-metastatic and resectable disease,
5. At least one lesion that can be biopsied for research purpose,
6. No prior treatment for the disease under study,
7. Age ≥ 18 years,
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1,
9. Life expectancy > 3 months,
10. Patients must have measurable disease (lesion in previously irradiated field can be considered as measurable if progressive at inclusion according to RECIST v1.1) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan.
11. Adequate hematological, renal, metabolic and hepatic function: a. Hemoglobin ≥ 8.0 g/dl; leucocytes ≥ 2.0 G/l, absolute neutrophil count (ANC) > 1.0 G/l and platelet count > 100 G/l, b. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normality (ULN) , c. Total bilirubin ≤ 1.5 x ULN d. Albumin ≥ 25g/l e. Serum creatinine ≤ 1.5 x ULN OR Calculated creatinine clearance (CrCl) ≥ 60 ml/min (calculated per institutional standard) for subject with creatinine levels > 1.5 x ULN. f. Thyroid function within normal laboratory ranges (TSH, free T3, free T4)
12. Left ventricular ejection fraction (LVEF) ≥ 50% assessed by ECHO or MUGA within 6 months from study entry,
13. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry. Pregnancy test (serum or urine) should be repeated within 72 hours prior to receiving the first dose of trial medication.
14. Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for one year after discontinuation of treatment for women and 4 months for men.
15. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, concomitant endometrial carcinoma stage IA grade 1, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
16. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5),
17. Voluntarily signed and dated written informed consent prior to any study specific procedure,
18. Patients with a social security in compliance with the French law,
19. Patients for whom an indication of neoadjuvant chemotherapy has been confirmed during a sarcoma multidisciplinary tumor board labelled by the French NCI (Réseau NETSARC+).

Exclusion criteria 21

1. Previous treatment for sarcoma including surgery, chemotherapy or radiotherapy
2. Previous treatments with doxorubicin, daunorubicin, epirubicin, idarubicin and/or other anthracyclines or anthracenediones at the maximum cumulative dose,
3. Known hypersensitivity to any involved study drug or any of its formulation components,
4. Has an active or ongoing infection requiring systemic therapy,
5. Known central nervous system malignancy (CNS),
6. Women who are pregnant or breast feeding,
7. Has known active hepatitis B or hepatitis C,
8. Has a known history of Human Immunodeficiency Virus (HIV),
9. Previous enrolment in the present study
10. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
11. Has received a live attenuated vaccine or a live vaccine within 30 days prior to the first dose of trial treatment, Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
12. Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: a. Myocardial infarction or stroke/transient ischemic attack within the 6 months prior to study entry. b. Uncontrolled angina within the 3 months prior to study entry. c. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes, or poorly controlled atrial fibrillation). d. Corrected QT (QTc) prolongation > 480 msec. e. History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled venous thrombus).
13. Uncontrolled or significant renal disease including, but not limited to, any of the following: a. Acute or uncontrolled urinary infection at study entry, b. Hemorrhagic cystitis at study entry, c. Presence of blood on dipstick at study entry, d. Vesical atony, e. Known urinary tract obstruction.
14. Patients with known history of active inflammatory bowel diseases, including those with small or large intestine inflammation, such as Crohn’s disease or ulcerative colitis, will be excluded from the study,
15. Has received systemic antibiotics within 14 days before the first dose of study treatment. Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
16. History of organ transplant, including allogeneic stem cell transplantation.
17. Receiving probiotics as of the first dose of study treatment.
18. Has an active autoimmune disease - Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible, - Patients requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at dose ≤ 10 mg or 10 mg equivalent prednisone day, - Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, intra-articular or inhalation) are acceptable.
19. Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
20. Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities (to Grade >1 or baseline), not require corticosteroids for this purpose, and not have had radiation pneumonitis.
21. Person under judicial protection or deprived of liberty.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The antitumor activity of retifanlimab (INCMGA00012) when prescribed in association with neoadjuvant chemotherapy (Doxorubicin + Ifosfamide) will be assessed based on histological response defined as less than 10% of viable tumor cells on surgical sample.

Secondary endpoints 3

1. Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first. 1- and 3-year PFS rates and median PFS will be reported.
2. Overall Survival (OS) is defined as the time from study treatment initiation to death (of any cause). 1- and 3-year OS rates and median OS will be reported.
3. Safety will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) from the NCI v5.0. Toxicity will be graded using the CTCAE v5.0. Adverse events, serious and non-serious, will be coded as per the MedDRA dictionary.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Bergonie

Sponsor organisation

Institut Bergonie

Address

229 Cours De L Argonne

City

Bordeaux

Postcode

33000

Country

France

Scientific contact point

Organisation

Institut Bergonie

Contact name

Pr Antoine ITALIANO

Public contact point

Organisation

Institut Bergonie

Contact name

Aurore Barthod-Malat

Locations

1 EU/EEA country · 2 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 6 files

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

Application history

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