Study Evaluating the Safety and Efficacy of MEDI5752 in Combination With Stereotactic Radiotherapy in Patients With Metastatic Sarcoma

NCT05821231 | Active Not Recruiting Phase 1

• 1 other identifier: 21SARC04
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

This is a phase I, multicenter, open-label study starting with a dose exploration phase and followed by an expansion phase to evaluate the safety profile and the preliminary activity of the bispecific antibody anti PD-1/CTLA-4 MEDI5752 in combination with SBRT delivered on one lung metastatic lesion, in patients with metastatic soft tissue sarcoma. Dose exploration phase: The primary objective of this dose exploration phase I trial is to determine the Maximum Tolerated Dose and the toxicity profile of MEDI5752 when administrated with stereotactic radiotherapy in patients with metastatic sarcoma with lung metastases. Expansion phase: The primary objective of the expansion phase is to investigate preliminary activity of MEDI5752 when administrated with stereotactic radiotherapy in patients with metastatic sarcoma with lung metastases. A maximum of 20 evaluable patients will be included in this trial.

Conditions

Soft Tissue Sarcoma

Keywords

Soft Tissue Sarcoma; Lung metastasis; Bispecific antibody anti PD-1/CTLA-4; Stereotactic body hypo-fractionated radiotherapy

Outcome Measures

Primary Outcomes (2)

• Dose exploration Phase: The incidence of the Dose-limiting toxicity (DLT)

  For each patient, DLT incidence will be evaluated during the first cycle.

  6 weeks after the last dose of radiotherapy for each patient

• Expansion phase: the rate of patients alive and without progression at 3 months.

  3 months post treatment for each patient

Secondary Outcomes (6)

• Dose exploration and Expansion Phases: The incidence of Treatment-Emergent Adverse Events will be evaluated using the NCI-CTCAE Version 5.0.

  15 months for each patient

• Dose exploration and Expansion Phases: Objective Response Rate (ORR) defined as the rate of patients with an objective response (i.e. CR or PR according to RECIST v1.1 criteria).

  15 months for each patient

• Dose exploration and Expansion Phases: Progression-Free Survival (PFS) defined (per RECIST v1.1 criteria) as the time from treatment initiation until progression or death from any cause, whichever occurs first.

  15 months for each patient

• Dose exploration and Expansion Phases: Time to progression of irradiated lesions defined as the time from treatment initiation until progression of irradiated lesions or death from any cause.

  15 months for each patient

• Dose exploration and Expansion Phases: Time to progression outside the irradiation field defined as the time from treatment initiation until progression outside the irradiation field or death from any cause.

  15 months for each patient

Study Arms (1)

Patients with metastatic soft tissue sarcoma with lung metastases

EXPERIMENTAL

Combination Product: SBRT + MEDI5752

Interventions

SBRT + MEDI5752 COMBINATION_PRODUCT

SBRT (5 fractions of 10 Gy every two or three days) will be delivered to one lung metastasis (12 days maximum) in combination with MEDI5752\* administered intravenously. The first dose of MEDI5752 will be administered on the day of the last SBRT fraction, then every 3 weeks for up to a maximum of 12 months. \* Dosing 500 mg or 750 mg, according to the recommended dose determined during the dose exploration phase

Patients with metastatic soft tissue sarcoma with lung metastases

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed soft tissue sarcoma of following subtype: undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, pleomorphic rhabdomyosarcoma, or pleomorphic liposarcoma
• Patients with metastatic disease, including (but not restricted to) lung metastasis (in case of lung metastasis only, patients must have more than 5 metastases measurable by RECIST 1.1)
• Patient with at least two metastases measurable by RECIST 1.1, including at least one lung metastasis amenable for SBRT, defined as following:
• Tumor size between 1cm and 3 cm, AND
• Peripheral tumor located further than 2 cm of the proximal bronchial tree (carina, right and left main bronchi, and bronchial tree to the second bifurcation)
• Metastatic disease pretreated by at least one anthracycline based chemotherapy, but no more than 3 lines of standard therapy
• Age ≥ 18 years at time of study entry
• ECOG performance status of 0 or 1
• Body Weight \> 35 kg
• Life expectancy of at least 3 months
• Previous treatment ended at least 4 weeks prior to first dose
• Adequate Hematology laboratory data within 28 days prior to start of treatment: Absolute neutrophils ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9 g/dL
• Adequate Biochemistry laboratory data within 28 days prior to start of treatment: Total bilirubin ≤ 1.5 x ULN (except patient with confirmed Gilbert's syndrome or liver metastasis: Total bilirubin ≤ 3 X ULN), Transaminases ≤ 3 x ULN, Alkalin phosphatases ≤ 5 x ULN, Creatinine clearance ≥ 45 mL/min (Cockcroft)
• Adequate cardiac function defined as follow: LVEF (as assessed by echocardiography or multiple-gated acquisition scan) ≥ 50% / Troponin I or T ≤ ULN (per institutional guidelines and/or not clinically significant per investigator judgement) / QTcF ≤ 480msec
• Women should be post-menopaused or willing to accept the use of at least one highly effective method of birth control from screening to 90 days after the last dose of MEDI5752. All non-menopaused women should have a negative pregnancy test within 72 hours prior to study dosing. Men should accept to use an effective contraception from screening to 90 days after the last dose of MEDI5752

You may not qualify if:

• Patients with no lung metastases amenable for SBRT
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to use effective birth control from screening to 90 days after the last dose of MEDI5752
• Any malignancy other than the disease under study in the past 2 years excepting curatively treated skin cancers such as Basal Cell Carcinoma or Squamous Cell Carcinoma.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled hypercalcemia (\> 1.5 mmol/L ionized calcium or Ca \> 12 mg/dL or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
• Severe, active co-morbidity, defined as follows:
• Unstable angina, uncontrolled cardiac arrhythmia, uncontrolled hypertension, symptomatic congestive heart failure
• Transmural myocardial infarction within the last 6 months prior to registration
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Uncontrolled Chronic Obstructive Pulmonary Disease or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease
• Known HIV positive status (positive for HIV-1 or HIV-2 antibodies)
• End-stage renal disease (i.e., on dialysis or dialysis has been recommended)

Sponsors & Collaborators

• Institut Claudius Regaud: lead
• National Cancer Institute, France: collaborator
• AstraZeneca: collaborator

Study Sites (5)

Institut Bergonié

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

Institut Regional Du Cancer de Montpellier

Montpellier, France

Location

IUCT-O

Toulouse, France

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2023
• First Posted: April 20, 2023
• Study Start: December 12, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 31, 2025

Record last verified: 2025-07

Locations

FR (5)