A clinical study of Tebentafusp alone or in combination with Pembrolizumab in suitable participants with pre-treated advanced melanoma.
Zusammenfassung der Studie
Tebentafusp is approved for the treatment of uveal melanoma (melanoma that starts in the eye). In this study, Tebentafusp is an experimental medication, meaning it has not yet been approved by a governmental authority for the treatment of the melanoma types being studied in this trial. The investigational drug helps T-cells (part of the body's immune system) bind to cancer cells that express the markers "HLA-A*02:01" and "gp100" and attack them. This is an open-label study, meaning you will know which treatment you will receive. The study consists of 3 treatment arms. Participants will be assigned equally to the treatment arms: In Arm A, treatment will be with Tebentafusp as monotherapy (single drug). In Arm B, Tebentafusp will be given in combination with Pembrolizumab, another approved medication. Arm C is a choice of other suitable treatments made by the investigator. Options include other standard drug treatments, best supportive care, and other clinical trials for which you would meet the inclusion criteria (except for studies sponsored by Immunocore). The main goal of the study is to investigate whether Tebentafusp improves survival compared to the therapy chosen by the investigator.
(BASEC)
Untersuchte Intervention
The study is divided into Phase II and Phase III:
In Phase II of the study, approximately 120 participants will be enrolled and randomly assigned to one of the treatment arms based on a set of predefined criteria. The allocation will be 1:1:1, meaning approximately 40 participants will be enrolled in each treatment arm. This approach aims to ensure the homogeneity of the treatment groups.
After the 120th patient is assigned in Phase II, Phase III of the study will begin. Participants will again be randomly assigned to treatment groups. However, these treatment groups may change based on the data observed in Phase II of the study. In Phase III of this study, approximately 510 participants are expected to be enrolled.
Each phase of this clinical study consists of 3 main sections: pre-screening/screening section, drug administration and treatment section, and follow-up section regarding survival. These sections will be described in more detail below. Pre-screening/screening section: All participants will take part in this section. This section begins after you have signed the patient information and consent form, in which you confirm that you understand the study and wish to participate. In this section, the investigator will review your medical records and examine you to ensure that this study is appropriate for you and that you meet the criteria for participation. As part of this process, various blood tests and radiological examinations (CT, MRI, etc.) will be performed. Additionally, a biopsy of your tumor tissue will be required unless an archived sample is available. After these examinations are completed, you will be randomly assigned to one of the treatment groups in the drug administration and treatment section of the study.
Drug administration and treatment section: Only participants in Arm A and Arm B of the study will undergo a treatment regimen with Tebentafusp (either Tebentafusp alone or Tebentafusp in combination with Pembrolizumab). Participants assigned to Arm C will receive a treatment determined by their treatment team. This may include another clinical trial or local standard treatments. During this time, all participants must attend the scheduled study visits for drug treatment and assessment. At certain times and intervals, as well as depending on the assigned treatment arm, additional blood samples and radiological examinations will be performed. Participants will remain in this section until disease progression occurs or further treatment is no longer possible due to safety or tolerability concerns. The maximum treatment duration is 2 years.
Follow-up section regarding survival: A follow-up regarding survival will be conducted on all participants. The follow-up will continue until the participants' death to determine whether treatment with Tebentafusp prolongs survival. During this section, participants will receive other suitable therapies, both approved and experimental.
(BASEC)
Untersuchte Krankheit(en)
Melanoma (a type of skin cancer) that has spread or cannot be surgically removed and has worsened after standard treatments. This study includes patients with melanomas from all parts of the body, except the eye.
(BASEC)
• 18 years of age or older • HLA-A*02:01 positive • Unresectable non-ocular melanoma stage III or IV • A freshly obtained (preferably) or archived tumor tissue sample has been provided (BASEC)
Ausschlusskriterien
• Diagnosis of ocular or metastatic choroidal melanoma • History of a malignant disease not treated in this study (with exceptions) • Unfit for re-treatment with Pembrolizumab due to a treatment-related AE during a previous treatment with an anti-PD(L)1 regimen • Known untreated or symptomatic central nervous system metastases and/or carcinomatous meningitis • Previous severe hypersensitivity reaction to treatment with another monoclonal antibody. • Clinically significant lung disease or impaired lung function • Clinically significant heart disease or impaired heart function • Active autoimmune disease requiring immunosuppressive treatment within 2 years of the pre-screening • Patients who have not received the required cancer therapies (BASEC)
Studienstandort
St Gallen, Zürich
(BASEC)
Sponsor
Immunocore Ltd IQVIA AG, Branch Basel
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Dr. med. Egle Ramelyte
+41 44 255 25 07
egle.ramelyte@clutterusz.chUniverstitätsSpital Zürich, Klinik für Dermatologie
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
13.10.2023
(BASEC)
ICTRP Studien-ID
NCT05549297 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination with Pembrolizumab Versus Investigator’s Choice in HLA-A*02:01-positive Participants with Previously Treated Advanced Melanoma (TEBE-AM) (BASEC)
Wissenschaftlicher Titel
Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination With Pembrolizumab Versus Investigator's Choice in HLA-A*02:01-positive Participants With Previously Treated Advanced Melanoma (TEBE-AM) (ICTRP)
Öffentlicher Titel
Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM) (ICTRP)
Untersuchte Krankheit(en)
Advanced Melanoma (ICTRP)
Untersuchte Intervention
Drug: TebentafuspDrug: Tebentafusp with PembrolizumabDrug: Investigators Choice (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria:
- HLA-A*02:01-positive
- unresectable Stage III or Stage IV non-ocular melanoma
- archival tumor tissue sample or a newly obtained biopsy of a tumor lesion not
previously irradiated has been provided.
- measurable or non-measurable disease per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- If applicable, must agree to use highly effective contraception
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the Informed Consent (ICF) and protocol
- Must agree to provide protocol specified samples for biomarker analyses.
Exclusion Criteria:
- Pregnant or lactating women
- diagnosis of ocular or metastatic uveal melanoma
- history of a malignant disease other than those being treated in this study
- ineligible to be retreated with pembrolizumab due to a treatment-related AE
- known untreated or symptomatic central nervous system (CNS) metastases and/or
carcinomatous meningitis
- previous severe hypersensitivity reaction to treatment with another monoclonal
antibody (mAb)
- active autoimmune disease requiring immunosuppressive treatment
- clinically significant cardiac or pulmonary disease or impaired cardiac function
- known psychiatric or substance abuse disorders
- received prior treatment with a licensed or investigative Immune-mobilizing
monoclonal T-cell receptor Against Cancer (ImmTAC) medication or who have not
completed adequate washout from prior medications.
- received chemotherapy or biological cancer therapy (excluding anti-PD(L)1 mAb,
ipilimumab, and BRAF TKI regimen) within 14 days of first dose
- received cellular therapies within 90 days of study intervention
- ongoing Common Terminology Criteria for Adverse Events(CTCAE) Grade = 2 clinically
significant who in the opinion of the investigator could affect the outcome of the
study
- received systemic treatment with steroids or any other immunosuppressive drug within
2 weeks of first dose
- have not progressed on treatment with an anti-PD(L)1 mAb
- have not received prior treatment with an approved anti-CTLA-4 mAb
- a BRAF V600 mutation, who have not received a prior BRAF/MEK TKI regimen
- currently participating or have participated in a study of an investigational agent
or using an investigational device within 30 days of the first dose
- known history of chronic viral infections such as hepatitis B virus (HBV) or
hepatitis C virus (HCV)
- known clinically significant pulmonary or cardiac disease or impaired lung or
cardiac function
- Out of range Laboratory values
- history of allogenic tissue/solid organ transplant (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Overall Survival (OS) (ICTRP)
Change from Baseline in Circulating Tumor DNS (ctDNA);Number of participants with =1 adverse event (AE);Number of participants with =1 serious adverse event (SAEs);Number of participants with dose interruptions, reductions, and discontinuations from study therapy due to AEs;Number of participants with Grade =2 cytokine release syndrome (CRS);Responses to the EORTC Core Quality of Life (EORTC-QLQ-C30);Responses to the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L);Plasma Concentration of Tebentafusp;Number of participants with anti-tebentafusp antibodies (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Immunocore Medical Information, medical.information@immunocore.com, 844-466-8661 (ICTRP)
Sekundäre IDs
IMCgp100-203 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT05549297 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar