Overview
A Multicentric Phase II Trial Evaluating MEDI5752 in Patients With Mature Tertiary Lymphoid Structures Solid Tumors.
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2027-09-01
2027-09-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II trial assessing the efficacy of MEDI5752Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Institut BergoniéCollaborators:
AstraZeneca
National Cancer Institute, France
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.