Sacituzumab Govitecan and Bevacizumab for NSCLC Brain Metastases

NCT06401824 | Recruiting Phase 2 DMC

• 1 other identifier: CO-NL-979-6888
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate whether the combination of sacituzumab govitecan (SG) and bevacizumab will result in shrinkage of brain metastases from patients with non-squamous non-small cell lung cancer (NSCLC), with disease progression on chemotherapy and immunotherapy.

Conditions

NSCLC Stage IV; Brain Metastases, Adult

Keywords

non small cell lung cancer; brain metastases; bevacizumab; sacituzumab govitecan

Outcome Measures

Primary Outcomes (1)

• brain metastases overall response rate (ORR)

  ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) based on central and local investigator's assessment according to RANO-BM criteria on brain MRI

  up to 24 months

Secondary Outcomes (8)

• brain metastases overall response rate (ORR) with correction for bevacizumab-pseudoresponse

  up to 24 months

• brain metastases disease control rate (DCR)

  up to 24 months

• CNS progression free survival (PFS)

  up to 24 months

• Extracranial ORR and DCR

  up to 24 months

• Extracranial PFS

  up to 24 months

Study Arms (1)

sacituzumab govitecan (SG) plus bevacizumab

EXPERIMENTAL

SG 10mg/kg intravenous day 1 and day 8 of a 21-day cycle, + bevacizumab 15 mg/kg iv day 1 of a 21-day cycle till unacceptable toxicity or disease progression.

Drug: Sacituzumab Govitecan-Hziy 180 MG plus bevacizumab

Interventions

Sacituzumab Govitecan-Hziy 180 MG plus bevacizumab DRUG

Sacituzumab govitecan 10mg/kg intravenous day 1 and day 8 of a 21-day cycle, + bevacizumab 15 mg/kg iv day 1 of a 21-day cycle till unacceptable toxicity or disease progression.

Also known as: sacituzumab govitecan; zirabev

sacituzumab govitecan (SG) plus bevacizumab

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Signed informed consent must be obtained prior to participation in the study.
• Participant is an adult ≥ 18 years of age at the time of informed consent.
• ECOG performance status ≤1.
• Estimated life expectancy of 12 weeks or more.
• Pathology proven metastatic non-squamous NSCLC
• For those without an actionable oncogenic driver: progression on immunotherapy and/or platinum-doublet chemotherapy (concurrent or sequential, in any order). If contra-indication for immunotherapy: progression on platinum-doublet chemotherapy.
• For those with an actionable oncogenic driver: progression on targeted therapy and platinum-doublet chemotherapy. For the latter group, previous ICI is allowed but not mandatory.
• BM not in eloquent area (all patients have at least to be discussed with a neurologist, and preferably they are discussed in the local neuro-oncology MDT).
• Maximum BM size 2 cm in longest diameter (for each BM).
• At least one untreated brain metastasis ≥ 5mm:
• Patients with largest measurable intracranial lesion ≥5 mm but \<10 mm may be allowed to enroll upon agreement with the principal investigator (for patients with target lesions of ≥ 5mm but \<10 mm, 1.5 mm slice thickness brain MRI is required).
• Prior local treatment is permissible provided unequivocal progression in the lesion has since occurred (discussed in neuro-oncology MDT) or if new lesions have occurred.
• For at least 7 days prior to first dose of SG and bevacizumab in this study: Patient must be asymptomatic from CNS metastases and on a stable dose of corticosteroids, with a maximum of 4 mg dexamethasone/day. Anti-epileptic dose should also be stable for 7 days.
• Participant must have recovered from all toxicities related to prior treatments to grade ≤ 1 (CTCAE v 5.0). Exception to this criterion are alopecia and neuropathy of any grades.

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Leptomeningeal metastasis (based on MRI or CSF cytology, if strong suspicion despite negative MRI, CSF analysis should be done).
• Previous treatment with TROP2 inhibitor or angiogenesis inhibitor.
• Known hypersensitivity to the study drugs, its metabolites, or formulation excipient.
• Positive serum pregnancy test or women who are breastfeeding.
• Contra-indication for MRI.
• History of allogeneic bone marrow or solid organ transplant.
• Have had a prior anticancer biologic agent (ADC, ICI) within 4 weeks prior to enrolment or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrolment and have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs at the time of study entry.
• a. Note: Patients participating in observational studies are eligible.
• Have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs due to a previously administered agent.
• Note: patients with any grade vitiligo or alopecia are an exception to this criterion and will qualify for the study.
• Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Have an active second malignancy. Note: patients with a history of malignancy that has been treated completely, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumours with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.
• Met any of the following criteria for cardiac disease:
• Myocardial infarction or unstable angina pectoris within 6 months of enrollment.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Gilead Sciences: collaborator

Study Sites (3)

NKI-AvL

Amsterdam, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, Netherlands

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Bevacizumab; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lizza Hendriks, MD, PhD

  Maastricht University Medical Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lizza Hendriks, MD, PhD

CONTACT

+31(0)43-3875047; lizza.hendriks@mumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2024
• First Posted: May 7, 2024
• Study Start: April 24, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)