Phase 1/2 Study of SBRT With or Without GC4711 for NSCLC

• ClinicalTrials.gov Identifier: NCT04476797
• Recruitment Status: Recruiting
• First Posted: July 20, 2020
• Last Update Posted: March 18, 2021
• Sponsor: Galera Therapeutics, Inc.
• Information provided by (Responsible Party): Galera Therapeutics, Inc.

Tracking Information

• First Submitted Date: July 15, 2020
• First Posted Date: July 20, 2020
• Last Update Posted Date: March 18, 2021
• Actual Study Start Date: October 18, 2020
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 15, 2020)

• Number of dose-limiting toxicities during treatment and within 30 days post SBRT [ Time Frame: DLT 30 days post SBRT ]
  Phase 1
• DLCO measured by RTOG scale 3 months after completion of SBRT compared to baseline [ Time Frame: DLCO 90 days post SBRT ]
  Phase 2

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 1/2 Study of SBRT With or Without GC4711 for NSCLC
• Official Title: Phase 1/2 Study of Stereotactic Body Radiation Therapy (SBRT) With or Without GC4711 for Early Stage, Centrally Located or Large Non-Small Cell Lung Cancer (NSCLC)
• Brief Summary: GTI-4711-101 is a Phase 1-2 study of the safety of GC4711, and its potential to reduce radiation-related pulmonary injury due to SBRT for early stage large or central localized NSCLC. After an open-label, Phase 1, safety cohort of approximately 5 subjects has been completed, a randomized, double-blind, placebo-controlled Phase 2 portion will be conducted.

Detailed Description

Subjects must be referred for SBRT with large (>3cm) or central localized, node negative, non-metastatic NSCLC, and have an ECOG PS score of 0-3 to be considered for enrollment. Subjects with small peripheral lesions(≤3cm) are excluded, as the aim is to improve outcome in larger, central NSCLC carrying a higher risk of pneumonitis, as well as poorer local control. Feasibility of SBRT is judged by the treating physician. Chemotherapy given before SBRT is permitted, but subjects must be immunotherapy naive.

SBRT is planned on the (persistent) PET+ tumor location for a dose of 10-12 Gy in 5 fractions, delivered on sequential weekdays. In the Phase 1, 5 subjects will each receive GC4711 by 15-minute IV infusion, before each SBRT fraction After the Phase 1, a Phase 2, randomized, double-blind, placebo-controlled study phase will be initiated, wherein approximately 66 subjects referred for SBRT with early stage large or central localized NSCLC will be randomized in a 1:1 ratio to receive either GC4711 or placebo given intravenously (IV) before each fraction of SBRT.

All subjects will be evaluated for changes in the diffusion capacity of carbon monoxide (DLCO) and pneumonitis. All subjects will be followed for 12 months for treatment related adverse effects, disease control (Progression Free Survival (PFS), Overall Survival (OS), Distant Metastases (DM) rate and local control-(RECSIST 1.1), and quality of life (FACT-L) A Data Monitoring Committee will be established for the Phase 2 portion of the study to provide independent monitoring of safety given the blinded design.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• SBRT
• NSCLC
• Non-metastatic

Intervention

• Drug: GC4711
  15 minute IV Infusion
• Drug: Placebo
  15 minute IV infusion

Study Arms

• Experimental: Arm A Active GC4711
  Intervention: Drug: GC4711
• Placebo Comparator: Arm B Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 15, 2020): 71
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female subjects at least 18 years of age.
2. Ability to understand and the willingness to sign a written informed consent.
3. Histological or biopsy proven NSCLC. For peripheral lesions, cytology and/or clear imaging-guided suspicion is accepted if histology cannot be obtained.
4. ECOG performance status of 0-3.
5. Large (>3cm) or centrally localized (within 2cm in all directions around the proximal bronchial tree, including ultra-central tumors, abutting the bronchial tree or trachea), node negative and non-metastatic NSCLC, judged acceptable for SBRT by the treating Investigator. Staged with FDG-PET/CT, brain CT or MRI with contrast and/or mediastinoscopy, measurable disease as defined by RECIST 1.1.

6. Adequate end-organ function, based on routine clinical and laboratory workup:

   1. ANC >1,000 cells/µl, Platelets ≥ 75,000 cells/µl, Hemoglobin ≥ 8.0 g/dl
   2. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min
   3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN
   4. International normalized ratio (INR) (or prothrombin time (PT)) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, if values are within the intended therapeutic range
7. Males and females of must agree to use effective contraception starting prior to the first day of treatment and continuing after the last dose of GC4711/Placebo for 30 days (females) and 90 days (males).

Exclusion Criteria:

1. Subjects with confirmed nodal and/or distant disease(including brain), according standard workup by local investigator
2. Subjects with peripheral lesions 3cm or smaller
3. Prior treatment with immunotherapy
4. Prior intra-thoracic radiotherapy or surgery with substantial overlap in former radiation fields as determined by the treating radiation oncologist.
5. Subjects not recovered/controlled from prior treatment-related (chemotherapy or targeted therapy) toxicities judged by treating physician.
6. Uncontrolled malignancy other than lung cancer that requires active treatment or is deemed by the treating physicians to be likely to affect the subject's survival duration.
7. Subjects unable to lie down with arms up with a regular breathing pattern.
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to GC4711.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
10. Participation in other clinical trials either to treat diagnosed lung cancer or to reduce the toxicity of therapy from participating in GC4711 clinical trial.
11. Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure.
12. Female subjects who are pregnant or breastfeeding.
13. Any other conditions that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Melissa Brookes; 610-725-1500; info@galeratx.com

Contact: Charlotte Moser, MD, PhD; 610-725-1500; info@galeratx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04476797
• Other Study ID Numbers: GTI-4711-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Galera Therapeutics, Inc.
• Study Sponsor: Galera Therapeutics, Inc.
• Collaborators: Not Provided

Investigators

• Study Chair: Charlotte Moser, MD, PhD; VP, Clinical Development

• PRS Account: Galera Therapeutics, Inc.
• Verification Date: March 2021