MEDI5752 in Patients With Mature Tertiary Lymphoid Structures Solid Tumors.

Advanced Solid Tumor Clinical Trial

— TAYLOR  

Official title:

A Multicentric Phase II Trial Evaluating MEDI5752 in Patients With Mature Tertiary Lymphoid Structures Solid Tumors.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05888857
• Other study ID #: IB2023-01
• Secondary ID: 2023-503451-94
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2023
• Est. completion date: September 2027

Study information

• Verified date: May 2023
• Source: Institut Bergonié
• Contact: Antoine ITALIANO, MD, PhD
• Phone: +33556333333
• Email: a.italiano[@]bordeaux.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II trial assessing the efficacy of MEDI5752

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 102
• Est. completion date: September 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• MEDI5752
A treatment cycle consists of 3 weeks. MEDI5752 will be administered by intravenous infusion at a fixed dose on Day 1 of each cycle

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux

Sponsors (3)

Lead Sponsor	Collaborator
Institut Bergonié	AstraZeneca, National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of the antitumor activity of MEDI5752 (independently for eah cohort)	Antitumor activity will be assessed in terms of objective response rate within 24 weeks based on RECIST v1.1, independently for each cohort, and based on centralized radiological review.; Objective response under treatment is defined as patients with confirmed complete response or confirmed partial response, as per RECIST v1.1, observed during treatment with the investigational product.; Objective response rate is defined as the proportion of patients alive with objective response based on RECIST v1.1.; Objective response is recorded from study treatment initiation until the end of treatment.	an expected average of 6 months
Secondary	24-weeks clinical benefit rate (CBR) independently for each cohort	CBR is defined as the proportion of patients with clinical benefit at 6 months. Clinical benefit is defined as confirmed complete response, confirmed partial response or stable disease more than 24 weeks, defined as per RECIST v1.1.	24 weeks
Secondary	Best overall response (BoR) independently for each cohort	BoR is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. The best overall response is determined once all the data for the participant is known (RECIST v1.1).	Throughout the treatment period, an expected average of 6 months
Secondary	Duration of response (DoR) independently for each cohort	DoR is defined as the time from documentation of tumor response (complete response/partial response whichever is first recorded) to disease progression, according to RECIST v1.1. DoR will be assessed in responder (confirmed CR / PR) patients only.	Throughout the treatment period, an expected average of 6 months
Secondary	1-year progression-free survival (PFS), independently for each cohort	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 year
Secondary	2-year progression-free survival (PFS), independently for each cohort	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	2 year
Secondary	1-year overall survival (OS), independently for each cohort	OS is defined as the time from study treatment initiation to death (of any cause)	1 year
Secondary	2-year overall survival (OS), independently for each cohort	OS is defined as the time from study treatment initiation to death (of any cause)	2 year
Secondary	Safety profile, independently for each cohort: Common Terminology Criteria for Adverse Events version 5	Number of participants with toxicity graded using the Common Terminology Criteria for Adverse Events version 5	Throughout the treatment period, an expected average of 6 months
Secondary	24-weeks clinical benefit rate (iCBR) independently for each cohort as per iRECIST	iCBR is defined as the rate of patients with iCR, iPR or immune stable disease (iSD)	24 weeks
Secondary	Duration of response (iDoR) independently for each cohort as per iRECIST	iDoR is defined as the time from the date of the first response iCR/iPR (whichever is first recorded) to the date of PD (iUPD confirmed as iCPD) as per iRECIST. iDOR is defined for subjects with iCR or iPR. If a patient has iPR (#1) followed by a iUPD (#1) which is not confirmed, then a iPR (#2) followed by a iUPD (#2) which is confirmed at the next assessment, then the iDOR is calculated from iPR1 until iUPD2	Throughout the treatment period, an expected average of 6 months
Secondary	1-year progression-free survival (iPFS), independently for each cohort as per iRECIST	o iPFS is defined as the time from study treatment initiation to the first occurrence of disease progression as per iRECIST or death (of any cause), whichever occurs first. The event date to be used for calculation of progression-free survival (iPFS) should be the first date at which progression criteria are met (ie, the date of iUPD) provided that iCPD is confirmed at the next assessment. If iUPD occurs, but is disregarded because of later iSD, iPR, or iCR, that iUPD date should not be used as the progression event date. If progression is not confirmed and there is no subsequent iSD, iPR, or iCR, then the iUPD date should still be used in the following scenarios: if the patient stops protocol treatment because they were not judged to be clinically stable, or no further response assessments are done (because of patient refusal, protocol noncompliance, or patient death); the next timepoint responses are all iUPD, and iCPD never occurs	1 year
Secondary	2-year progression-free survival (iPFS), independently for each cohort as per iRECIST	o iPFS is defined as the time from study treatment initiation to the first occurrence of disease progression as per iRECIST or death (of any cause), whichever occurs first. The event date to be used for calculation of progression-free survival (iPFS) should be the first date at which progression criteria are met (ie, the date of iUPD) provided that iCPD is confirmed at the next assessment. If iUPD occurs, but is disregarded because of later iSD, iPR, or iCR, that iUPD date should not be used as the progression event date. If progression is not confirmed and there is no subsequent iSD, iPR, or iCR, then the iUPD date should still be used in the following scenarios: if the patient stops protocol treatment because they were not judged to be clinically stable, or no further response assessments are done (because of patient refusal, protocol noncompliance, or patient death); the next timepoint responses are all iUPD, and iCPD never occurs	2 year
Secondary	iORR independently for each cohort	iORR is defined as the rate of patients with immune complete or partial responses (iCR, iPR) as per iRECIST. iCR and iPR can be assigned after iUPD (immune unconfirmed progressive disease) has been documented as per iRECIST (Seymour et al)	Throughout the treatment period, an expected average of 6 months