Molecularly Targeted Radionuclide Therapy Via the Integrin Alphavbeta6

Phase 1

Recruiting

• Conditions: Metastatic Nonsmall Cell Lung Cancer
• Interventions: Drug: [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G.

• Registration Number: NCT06228482
• Lead Sponsor: University of California, Davis

Brief Summary

This is a Phase I study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostics pair in patients with metastatic non small cell lung cancer (NSCLC).

Detailed Description

This is a Phase I study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostics pair in patients with metastatic NSCLC. \[68Ga\]Ga DOTA-5G PET/CT will be used to identify and stratify patients eligible for (and most likely to respond to) the \[177Lu\]Lu DOTA-ABM-5G therapy. Up to 40 patients will be enrolled over a 36-month period with metastatic NSCLC with a life expectancy of at least 3 months, who demonstrate disease progression after at least 1 prior treatment for metastatic disease and have available archival tissue.

We hypothesize that a) \[68Ga\]Ga DOTA-5G will detect lesions in patients with metastatic NSCLC, b) the theranostic pair \[68Ga\]Ga DOTA-5G/ \[177Lu\]Lu DOTA-ABM-5G will be safe and well tolerated, and c) a therapeutic response will be achieved with a single dose of \[177Lu\]Lu DOTA-ABM-5G.

Study Timeline

• Status Verified: 2024-01
• Study First Submitted: 2024-01-18
• Study First Submitted QC: 2024-01-18
• Study Start: 2024-01-22
• Study First Posted: 2024-01-29
• Last Update Submitted: 2024-01-30
• Last Update Posted: 2024-02-01
• Primary Completion: 2026-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

[68Ga]Ga DOTA-5G PET/CT Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent document.

2. Age 18 or more years

3. Pathologically confirmed NSCLC with metastatic disease and measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion > 1 cm or lymph node > 1.5 cm in short axis)

4. Participant must have documented tumor progression for metastatic disease during or following at least one prior FDA approved systemic regimen as established by diagnostic imaging.

5. Available archival tumor tissue (excisional, core, or FNA is acceptable). Tissue from a metastatic site is preferred when available.

6. Eastern Cooperative Oncology Group Performance Status ≤ 2

7. Participant must have completed prior systemic therapy at least 2 weeks (washout period) prior to [68Ga]Ga DOTA-5G PET scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved to Grade 1 or baseline.

8. Hematologic parameters defined as:

   Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 8 g/dL

9. Blood chemistry levels defined as:

   AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 2 times ULN Creatinine ≤ 2 times ULN

10. Anticipated life expectancy ≥ 3 months

11. Able to remain motionless for up to 30-60 minutes per scan

[177Lu]Lu DOTA-ABM-5G therapy Inclusion Criteria:

1. Completion of entry into [68Ga]Ga DOTA-5G PET study and completion of scan
2. The presence of at least one measurable disease by [68Ga]Ga DOTA-5G PET/CT (SUVmax>2-fold above normal bone, brain, lung or liver and identified on standard of care diagnostic imaging) Patients with a history of brain metastases and or any clinical concern for brain metastases will be evaluated with brain MRI as per standard of care for patients with metastatic NSCLC.

Exclusion Criteria

[68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G therapy Exclusion Criteria:

1. Participants with Class 3 or 4 NYHA Congestive Heart Failure
2. Clinically significant bleeding within two weeks prior to trial. entry (e.g. gastrointestinal bleeding, intracranial bleeding)
3. Pregnant or lactating women
4. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to study day 1 or anticipated surgery within the subsequent 6 weeks
5. Has an additional active malignancy requiring therapy within the past 2 years (other than early stage, surgically managed basal and squamous skin cancer and in situ malignancies of the breast and cervix)
6. Active, uncontrolled bacterial, viral, or fungal infection(s) despite systemic therapy
7. Psychiatric illness/social situations that would interfere with compliance with study requirements
8. Cannot undergo PET/CT or SPECT/CT scanning because of weight limits (350 lbs.)
9. Known interstitial lung disease or pre-existing pulmonary fibrosis
10. INR >2.0: PTT>15 seconds above ULN

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[177Lu]Lu DOTA-ABM-5G single dose therapy study	[68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G.	Patients will be undergo \[68Ga\]Ga DOTA-5G PET/CT scans to confirm eligibility for the \[177Lu\]Lu DOTA-ABM-5G therapy. Patients with sufficient lesion uptake of \[68Ga\]Ga DOTA-5G PET/CT will be offered therapy.

Primary Outcome Measures

Name	Time	Method
[68Ga]Ga DOTA-5G PET/CT imaging	2 hours from time of injection	To assess the ability of \[68Ga\]Ga DOTA-5G to detect lesions in patients with metastatic NSCLC
[177Lu]Lu DOTA-ABM-5G treatment	30 days from time of treatment	To assess the safety and tolerability of a single treatment with \[177Lu\]Lu DOTA-ABM-5G
[177Lu]Lu DOTA-ABM-5G treatment efficacy	60 days from time of treatment	To assess treatment efficacy (response vs. no response) assessed by comparison with a post-treatment scan (standard of care imaging and post second \[68Ga\]Ga DOTA-5G PET/CT, prior to next line of therapy.

Trial Locations

Locations (1)

The University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States