Trial Title:
MEDI5752 in Patients With Mature Tertiary Lymphoid Structures Solid Tumors.
NCT ID:
NCT05888857
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Tertiary Lymphoid Structures
Conditions: Keywords:
tertiary lymphoid structure
solid tumor
immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
2 independent single-arm, multicenter, phase II trials, based on a two-stage
three-outcome design as described in Sargent et al.
Cohort A : patients with TLS+ IO-naïve solid tumor (miscellaneous) Cohort B: patients
with TLS+ PD1/PDL1-experienced solid tumor (miscellaneous)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
MEDI5752
Description:
A treatment cycle consists of 3 weeks. MEDI5752 will be administered by intravenous
infusion at a fixed dose on Day 1 of each cycle
Arm group label:
Cohort A: patients with TLS+ IO-naïve solid tumors
Arm group label:
Cohort B: patients with TLS+ PD1/PDL1-experienced solid tumors
Summary:
Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II
trial assessing the efficacy of MEDI5752
Detailed description:
Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II
trial assessing the efficacy of MEDI5752.
Patients with mature tertiary lymphoid structures advanced solid tumors will be included
in two independent cohorts:
- Cohort A: patients with TLS+ IO-naïve solid tumor (miscellaneous)
- Cohort B: patients with TLS+ PD1/PDL1-experienced solid tumor (miscellaneous) Each
cohort will rely on a two-stage three-outcome design as described in Sargent et al.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed solid tumor
2. IO-naïve patients (cohort A) OR patients with secondary resistance to PD1/PDL1
inhibitors (cohort B),
3. Patients in cohort B:
1. have to be diagnosed previously treated with PD-L1/PD-1 inhibitors
(investigational or approved),
2. must have experienced initial clinical benefit (stable disease or better) from
checkpoint inhibitor therapy for at least 4 months in which there was at least
one interval scan prior to 4 months demonstrating no progression of disease.
4. Presence of mature tertiary lymphoid structures (TLS) by IHC as described in
protocol section 3.2.4. Except if presence of TLS has been already confirmed by
Biopathological platform at Bergonié Institute, presence of TLS should be confirmed
by central review based on FFPE tumor tissue sample,
5. Advanced unresectable or metastatic solid disease,
6. Measurable disease according to RECIST v1.1
7. At least one tumor site that can be biopsied for research purpose,
8. Age ≥ 18 years,
9. Body weight > 35 kg,
10. ECOG ≤ 1,
11. Life expectancy > 3 months,
12. Adequate hematological, renal, metabolic, hepatic and cardiac functions:
13. Disease progression on prior treatment, or previously untreated disease with no
available acceptable treatment. Note that no more than three lines of systemic
treatment for metastatic disease are allowed and that patients with oncogenic
addiction must have progressed on prior approved regimens),
14. Recovery to grade ≤ 1 from any adverse event derived from previous treatment
(excluding alopecia of any grade (according to the NCI-CTCAE, version 5.0),
15. Women of childbearing potential must have a negative serum pregnancy test within 7
days prior to study entry.
16. Women and men must agree to use at least one medically highly effective method of
contraception from screening, throughout the treatment period
17. Voluntary signed and dated written informed consents prior to any specific study
procedure,
18. Patients with a social security in compliance with the French law.
Exclusion Criteria:
1. Any anticancer treatment within 21 days or 5 half-lives (whichever is shorter) prior
to start of study treatment,
2. Whole brain radiotherapy within 14 days prior to start of study treatment,
3. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of the first dose of study drug.
4. Stereotactic radiosurgery within 7 days prior to start of study treatment,
5. Major surgery within 4 weeks prior to start of study treatment or still recovering
from prior surgery
6. Men or women of childbearing potential who are not using an effective method of
contraception as previously described; women who are pregnant or breast feeding,
7. History of or concurrent serious medical condition or abnormality in clinical
laboratory tests that, in the investigator's judgment, precludes the patient's safe
participation in and completion of the study or confounds the ability to interpret
data from the study
8. Prior or concurrent malignant disease
9. Any prior Grade ≥ 3 imAE while receiving immunotherapy or any unresolved imAE >
Grade 1
10. For subjects who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 : Subject
must not have experienced a toxicity that led to permanent discontinuation of prior
immunotherapy, must not have experienced a ≥ grade 3 imAE or an immune-related
neurologic or ocular AE of any grade while receiving prior immunotherapy, must not
have required the use of additional immunosuppression other than corticosteroids for
the management of an AE, must not have experienced recurrence of an AE if
rechallenged, and must not currently require maintenance doses of > 10 mg prednisone
or equivalent per day
11. Symptomatic or actively progressing central nervous system metastases.
12. History of leptomeningeal disease or cord compression
13. Uncontrolled or symptomatic hypercalcemia
14. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures
15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, cardiomyopathy of any etiology, symptomatic congestive heart failure,
uncontrolled hypertension, unstable angina pectoris, history of myocardial
infarction within the past 12 months, cardiac arrhythmia, ILD, serious chronic
gastrointestinal conditions associated with diarrhea,
16. Cerebrovascular accident within 6 months prior to enrolment,
17. Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal
therapy for cancer treatment.
18. Active or history of autoimmune disease immune deficiency or inflammatory disorders,
including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis,
systemic lupus erythematosus, sarcoidosis syndrome, rheumatoid arthritis,
hypophysitis, uveitis, inflammatory bowel disease, diverticulitis antiphospholipid
antibody syndrome, Wegener granulomatosis, Graves'disease, Sjögren syndrome,
Guillain-Barré syndrome, or multiple sclerosis,
19. History of idiopathic pulmonary fibrosis, organizing pneumonia drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on
screening CT scan.
20. Evidence of the following infections: active infection including tuberculosis, HIV,
active hepatitis B or C or A
21. Any contraindication to biopsy for the research,
22. Participation to a study involving a medical or therapeutic intervention in the last
30 days,
23. Patient unable to follow and comply with the study procedures because of any
geographical, social or psychological reasons,
24. Severe infection within 4 weeks prior to initiation of study treatment, including,
but not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia,
25. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment.
26. Prior allogeneic stem cell or solid organ transplantation,
27. Treatment with a live, attenuated vaccine within 30 days prior to initiation of
study treatment
28. Treatment with systemic immunosuppressive medication within 2 weeks prior to
initiation of study treatment, or anticipation of need for systemic
Immunosuppressive medication during study treatment,
29. History of severe allergic anaphylactic reaction to chimeric or humanized antibodies
or fusion proteins,
30. Known hypersensitivity to Chinese hamster ovary cell products, to any component of
the MEDI5752 formulation or to any human globulin therapy.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut Bergonie
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Contact:
Last name:
Antoine ITALIANO, MD, PhD
Email:
a.italiano@bordeaux.unicancer.fr
Start date:
September 2023
Completion date:
September 2027
Lead sponsor:
Agency:
Institut Bergonié
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute, France
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
Institut Bergonié
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05888857
