LAG3 PET; ImmunoPET imaging with 89Zr-DFO-REGN3767 in patients with advanced solid cancer prior to and during treatment with cemiplimab with or without platinum-based chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Nov 2024 → ongoing

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516795-15-00

EudraCT number

2020-004052-15

ClinicalTrials.gov

NCT04706715

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety

• To determine the optimal 89Zr-DFO-REGN3767 dose and optimal PET imaging timepoint.
• To evaluate the PK of 89Zr-DFO-REGN3767 by measuring SUV on 89Zr-DFO-REGN3767 PET scans in patients with histologically or cytologically documented locally advanced or metastatic solid tumors who, based on available clinical data, may benefit from treatment with cemiplimab +/- platinum-based chemotherapy.
• To evaluate safety of 89Zr-DFO-REGN3767.

Secondary objectives 4

1. To assess the heterogeneity of 89Zr-DFO-REGN3767 antibody tumor uptake within a lesion and between lesions
2. To correlate tumor tracer uptake with tumor and immune cell LAG3 expression as assessed by biopsy.
3. To correlate the tumor tracer uptake with response to cemiplimab with or without platinum-based chemotherapy.
4. To assess changes in tumor and normal organ uptake after 2 cycles of cemiplimab with or without chemotherapy

Conditions and MedDRA coding

Metastatic solid tumors, these may include but are not limited to melanoma, non-small-cell lung carcinoma (NSCLC), cervical cancer, microsatellite instable (MSI)-high/deficient mismatch repair (dMMR) cancer, renal cell carcinoma (RCC), CSCC, urothelial cell carcer (UCC), small cell lung cancer (SCLC) and head and neck squamous cell carcinoma (HNSCC).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age ≥ 18 years at the time of signing informed consent.
2. Patients with histologically confirmed diagnosis of locally advanced or metastatic solid cancer types who, according to the opinion of the investigator, based on available clinical data, may benefit from PD1 antibody with or without platinum based chemotherapy.
3. At least 1 lesion that is accessible per investigator’s assessment and eligible for biopsy according to standard clinical care procedures.
4. Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions except for lesions that have progressed after radiotherapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy ≥ 12 weeks.
7. Adequate organ and bone marrow function as defined below: a. Hemoglobin ≥9.0 g/dL b. Absolute neutrophil count ≥1.5 x 109 /L c. Absolute lymphocyte count ≥0.75 x 109 /L d. Platelet count ≥100 x 109 /L e. Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate > 30 mL/min/1.73 m2 . A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria. f. Adequate hepatic function: i. Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumor involvement); Patients with Gilbert’s syndrome do not need to meet total bilirubin requirements, provided their total bilirubin is unchanged from their baseline. Gilbert’s syndrome must be documented appropriately as past medical history. ii. Aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement) iii. Alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement) iv. Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or bone tumor involvement)
8. Signed informed consent.
9. Willingness and ability to comply with all protocol required procedures.

Exclusion criteria 20

1. Treatment with any approved anti-cancer therapy, investigational agent, or participation in another clinical trial with therapeutic intent within 28 days prior to 89Zr-DFO-REGN3767 injection.
2. Prior ICI treatment, including but not limited to anti-PD1 and anti-PD-L1 therapeutic antibodies in the past 12 months or ≥ 12 months ago, in case the ICI treatment was terminated for progressive disease or toxicity.
3. Encephalitis, meningitis, or uncontrolled seizures in the year prior to inclusion.
4. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
5. Symptomatic, untreated brain metastasis, leptomeningeal disease, or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurologically stable for at least 2 weeks prior to enrollment.
6. Documented allergic or acute hypersensitivity reaction attributed to antibody treatments
7. Major surgical procedure other than for diagnosis within 28 days prior to 89Zr-DFOREGN3767 injection or anticipation of need for a major surgical procedure during the course of the study.
8. For patients that will be treated with cemiplimab in combination with platinum containing chemotherapy, the following. • Cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), unstable angina, unstable cardiac arrhythmias, myocardial infarction < 3 months ago, or cerebrovascular accident < 6 months ago. • Hearing loss • Any other exclusion criteria, according to the local clinical practice guidelines for the chosen chemotherapy regimen. additional criteria apply: • Leucopenia <3 x 109 /L • Estimated glomerular filtration rate < 60 mL/min/1.73 m2
9. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for his study. • Patients with controlled type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
10. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
11. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks prior to 89Zr-DFO-REGN3767 injection. • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the sponsor. • The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
12. Prior allogeneic bone marrow transplantation or solid organ transplant.
13. Active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C or tuberculosis infection; or diagnosis of immunodeficiency • Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at screening. • Patients with known HIV infection who have controlled infection (undetectable viral load (HIV ribonucleic acid (RNA) polymerase chain reaction (PCR)) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards. • Patients with hepatitis B who have a controlled infection (serum HBV deoxyribonucleic acid (DNA) PCR below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug. • Patients who are HCV antibody-positive who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted. • Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
14. Active infection that requires systemic antibiotics within 2 weeks prior to 89Zr-DFOREGN3767 injection.
15. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of 89Zr-DFO-REGN3767, or that may affect the interpretation of the results or render the patient at high risk from complications.
16. Receipt of a live vaccine (including attenuated) within 30 days of planned start of study medication.
17. Altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
18. Sponsor employee/member of the clinical site study team and/or his or her immediate family
19. Women with a positive serum chorionic gonadotropin HCG pregnancy test at the screening/baseline visit. Breastfeeding women are also excluded.
20. Women of childbearing potential and sexually active men who are unwilling to practice highly effective contraception prior to the first dose of study therapy, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include: • stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening • intrauterine device (IUD); intrauterine hormone-releasing system (IUS) • bilateral tubal ligation • vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the women of childbearing potential (WOCBP) study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure) • and/or sexual abstinence

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Comparison of standardized uptake values in tumor lesions and tumor-to-blood ratios at different time points and different 89Zr-DFO-REGN3767 antibody dose levels.
2. To evaluate the biodistribution and PK of 89Zr-DFO-REGN3767 antibody by measuring standardized uptake value (SUV) on 89Zr-DFO-REGN3767 PET scans in patients with histologically or cytologically documented locally advanced or metastatic solid tumors who based on available clinical data may benefit from treatment with cemiplimab with or without platinum-based chemotherapy.
3. Safety evaluation through summaries of adverse events, changes in laboratory test results and changes in vital signs after exposure to 89Zr-DFO-REGN3767.

Secondary endpoints 4

1. Comparison of tracer uptake, expressed as standardized uptake values, in different tumor lesions within and between patients on 89Zr-PET scans.
2. Correlation of tumor tracer uptake with tumor and immune cell LAG3 expression as assessed by immunohistochemistry on a tumor biopsy sample.
3. Correlation of tumor tracer uptake with response to cemiplimab with or without platinum-based chemotherapy, according to RECIST v1.1.
4. Assessment of change in tumor and normal organ tracer uptake after 2 cycles of cemiplimab with or without chemotherapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

E.G.E. de Vries

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

E.G.E. de Vries

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications