Early detection of side effects in patients with metastatic melanoma receiving immune checkpoint inhibitor therapy by investigation of the CD8+ immune infiltrate using [89Zr]Zr-Df-IAB22M2C-PET

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

6 Sep 2022 → ongoing

Decision date (initial)

2024-03-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512219-37-00

EudraCT number

2021-004328-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Feasibility of the early detection of immune-mediated ICT side effects by semiquantitative assessment of CD8+ lymphocyte infiltration using noninvasive [89Zr]Zr-Df-IAB22M2C PET imaging.

Conditions and MedDRA coding

melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female patients ≥18 years of age at the time of signing the informed consent.
2. Patients with metastasized or irresectable melanoma.
3. Eastern Cooperative Oncology Group Performance (ECOG) Status ≤2.
4. Patients scheduled for ICT as recommended by the interdisciplinary tumor board.
5. Understand and voluntarily sign an informed consent document prior to any study related assessments/ procedures.
6. Able to adhere to the study visit schedule and other protocol requirements
7. Consent to practice double-barrier contraception until end of the study (28 days after last [89Zr]Zr-Df-IAB22M2C injection): Females of childbearing potential (FCBP1) and male patients with female partner of childbearing potential1 are willing to use highly effective contraceptive methods at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after end of study treatment after the last dose. Recommendations (CTFG Recommendations related to contraception and pregnancy testing in clinical trials. Version 1.1, 2020) for highly effective contraceptive methods are: a) combined hormonal contraception associated with inhibition of ovulation • oral • intravaginal • transdermal b) progestogen-only hormonal contraception associated with inhibition of ovulation • oral • injectable • implantable c) intrauterine device (IUD) d) intrauterine hormone - releasing system (IUS) e) bilateral tubal occlusion f) vasectomized partner (2) g) sexual abstinence (3) 1For the purpose of this document, a female is considered of childbearing potential (FCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. For the purpose of this document, a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 2Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success. 3In the context of the CTFG guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.

Exclusion criteria 10

1. Known hypersensitivity to [89Zr]Zr-Df-IAB22M2C or its components or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
2. Persistent toxicity (>Grade 2) according to Common Terminology Criteria for Adverse Events [CTCAE] version 5.0, caused by previous cancer therapy, excluding alopecia.
3. Clinical signs of active infection (>Grade 2 according to CTCAE version 5.0).
4. Major surgery within 4 weeks of starting study treatment. Patients must have recovered from any effects of major surgery.
5. Patients receiving any systemic chemotherapy or radiotherapy within 2 weeks prior to study treatment or a longer period depending on the defined characteristics of the agents used.
6. Heart failure NYHA III/IV.
7. Patients not able to declare meaningful informed consent on their own.
8. Women during pregnancy and lactation; female patients of childbearing potential or male patients with female partners of childbearing potential not willing to practice effective contraception by using a double-barrier method from Day 1 until 28 days postdose.
9. Male patients planning to donate sperm while participating in the study and for at least 28 days after end of study treatment.
10. Participation in other therapeutic clinical trials or observation period of competing trials.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of patients for whom [89Zr]Zr-Df-IAB22M2C PET-imaging was feasible.

Secondary endpoints 6

1. Number of patients who are affected by 3/4 (CTCAE) ICT related side effects with detectable differences in [89Zr]Zr-Df-IAB22M2C PET-imaging before and after the first cycle of ICT.
2. Absolute uptake of [89Zr]Zr-Df-IAB22M2C as assessed by PET imaging before the first cycle of ICT in the organs predisposed for immune related side effects and lymphatic tissue in the patients with autoimmune side effects grade 3/4 (CTCAE) induced by ICT compared to patients without grade 3/4 (CTCAE) autoimmune side effects of ICT.
3. % uptake difference of [89Zr]Zr-Df-IAB22M2C before and after the first cycle of ICT in the organs predisposed for immune related side effects and the lymphatic tissue in the patients with autoimmune grade 3/4 (CTCAE) side effects induced by ICT compared to patients without autoimmune side effects of ICT.
4. Number of patients with detectable differences in [89Zr]Zr-Df-IAB22M2C uptake before and after the first cycle of ICT in the tumors, metastasis or the lymphatic tissue, who are showing a clinical response to ICT.
5. Absolute uptake of [89Zr]Zr-Df-IAB22M2C before the first cycle of ICT in the tumors, metastasis and lymphatic tissue in the patients who are showing a clinical response to ICT compared to non-responders.
6. % uptake difference of [89Zr]Zr-Df-IAB22M2C uptake before and after the first cycle of ICT in the tumors and metastasis as well as in the lymphatic organs in patients who are showing a clinical response to ICT.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Prof. Dr. med. Christian la Fougère

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Prof. Dr. med. Christian la Fougère

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

Application history

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