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Malignant MelanomaPhase 1/2NCT02535078

Phase 1b/2 Study of the Combination of IMCgp100 With Durvalumab and/or Tremelimumab in Advanced Cutaneous Melanoma

A Phase 1/2 study testing Tebentafusp (IMCgp100) in people with Malignant Melanoma, run by Immunocore Ltd at 4 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study was a mixed phase Ib/II, multi-center, open-label study of tebentafusp (IMCgp100) as a single agent, and in combination with durvalumab and/or tremelimumab, in metastatic cutaneous melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
Tebentafusp (IMCgp100)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
4 sitesUnited States
Study dates
Nov 2015to 6 Sep 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years
  • Written informed consent must be obtained from all patients prior to any study procedures
  • Patients with advanced non-uveal melanoma defined as unresectable stage III or metastatic stage IV disease. Patients with acral or mucosal melanoma are acceptable. Patients with melanoma of unknown primary are acceptable for Phase 1b escalation cohorts (Arms 1 to 5) but are excluded in Phase 2. NOTE: Patients with the diagnosis of UM are excluded from all cohorts
  • Phase 1b (Arm 4 and Arm 5) and Phase 2: Patients with disease progression following initiation of treatment with an approved PD-(L)1 inhibitor. Patients with BRAF mutations should be refractory to approved BRAF-inhibitor if clinically feasible. CTLA 4 inhibition therapy is acceptable as a prior line of therapy or in combination with anti-PD-(L)1 therapy. For Phase 2, no prior chemotherapy in the advanced setting is permitted
  • Phase 1b Arms 1-3: no restriction on prior therapy
  • HLA-A*02:01 positive by central assay or by an 510K approved assay run in CLIA-certified laboratory
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  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy of at least 3 months
  • Phase 2 cohorts only: Patients must have measurable disease according to RECIST v1.1 criteria. Patients enrolled in Phase 1b cohorts may have either measurable or only non-measurable disease (ie, non-target lesion only)
  • Phase 1b (Arm 4) and Phase 2 cohorts only: Patients must have a site of disease amenable to biopsy (ie, must not also be a target lesion OR if a target lesion must be > 2cm), and be a candidate for tumor biopsy according to the treating institution's guidelines. NOTE: Phase 1b Arms 1-3 and 5 patients are not required to have disease accessible to biopsy
  • For Arms 1-3 only (ie, applies only to patients assigned to receive tebentafusp in combination with checkpoint inhibitor[s]): Those receiving prior immunotherapy must meet all the following conditions:
  • Must not have experienced an immune-related adverse event (irAE) where the irAE was the reason for permanent discontinuation of prior immunotherapy in the most recent prior treatment regimen
  • All irAEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or baseline prior to screening for this study. Must not have experienced a ≥ Grade 3 immune-related AE within the past 16 weeks or any Grade 4 life-threatening irAE (regardless of duration) or neurologic or ocular AE of any grade while receiving prior immunotherapy. (NOTE: Patients with endocrine AE of any grade are permitted to enroll if they are stably maintained on appropriate replacement therapy, but must have no history of adrenal crisis and be asymptomatic)
  • Patients currently receiving chronic corticosteroid treatment (longer than 8 weeks duration) for management of pre-existing AEs, or patients with a history of chronic corticosteroid treatment longer than 8 weeks duration for AEs within 6 months of screening are excluded

Who cannot join

  • Presence of untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or cord compression.
  • History of severe hypersensitivity reactions to study medications
  • History of treatment-related interstitial lung disease/pneumonitis
  • Impaired baseline organ function as evaluated by out-of-range laboratory values.
  • Clinically significant cardiac disease or impaired cardiac function
  • Active autoimmune disease or a documented history of autoimmune disease
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  • Recent (< 12 months of planned first dose of study treatment) active diverticulitis (Phase 1b combination arms)
  • Active infection requiring systemic antibiotic therapy. NOTE: Patients requiring systemic antibiotics for infection must have completed therapy before planned first dose of study treatment
  • Known history of human immunodeficiency virus (HIV) infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulation
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, currently requiring medical intervention, per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection requiring treatment with currently an unknown status. History of treated hepatitis is not exclusionary
  • Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years after completion of treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type
  • Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
  • Systemic anti-cancer therapy within 2 weeks of the planned first dose of study treatment. For cytotoxic agents that have major delayed toxicity and any prior immunotherapy approach, 3 weeks is indicated as washout period
  • Presence of NCI CTCAE ≥ Grade 2 toxicity (except alopecia, peripheral neuropathy, and ototoxicity, which are excluded if ≥ NCI CTCAE Grade 3) due to prior cancer therapy
  • Systemic treatment with steroids or any other immunosuppressive drug use within 4 weeks of the planned first dose of study treatment, with the following exceptions:
  • Treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone ≤ 12 mg daily or the equivalent.
  • Local steroid therapies (eg, optic, ophthalmic, intra-articular, or inhaled medications) are acceptable
  • Premedication for allergy to contrast reagent or premedication regimen instituted per protocol
  • Steroids for management of CNS metastases > 2 weeks prior to the planned first dose of study treatment
  • Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment
  • Major surgery as defined by the investigator within 2 weeks of the first dose of study treatment.
  • Radiotherapy within 2 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass
  • Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GMCSF, MCSF) ≤ 2 weeks prior start or study treatment. NOTE: Patients must have completed therapy with hematopoietic colony-stimulating factors at least 2 weeks before the first dose of study treatment is given. An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is not red blood cell transfusion dependent
  • Pregnant or breast-feeding women
  • Women of child-bearing potential who are sexually active with a non-sterilized male partner, unless they are using highly effective contraception during study treatment, and must agree to continue using such precautions for 1 week after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician.
  • Male patients must be surgically sterile or use double barrier contraception method and are not allowed to donate sperm from enrollment through treatment and for 3 months following administration of the last dose of study drug
  • Patients who are relatives or dependents of the investigator

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: A Phase Ib/II Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 in Combination With Durvalumab (MEDI4736) or Tremelimumab or the Combination of Durvalumab and Tremelimumab Compared to IMCgp100 Alone in Patients With Advanced Melanoma

This study was a mixed phase Ib/II, multi-center, open-label study of tebentafusp (IMCgp100) as a single agent, and in combination with durvalumab and/or tremelimumab, in metastatic cutaneous melanoma. The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and to evaluate the anti-tumor activity of tebentafusp (IMCgp100) in combination with durvalumab (MEDI4736, programmed death-ligand 1 [PD-L1] inhibitor), tremelimumab (CLTA-4 inhibitor), and the combination of durvalumab with tremelimumab compared to single-agent tebentafusp (IMCgp100) alone administered as an intravenous or subcutaneous. The study will enroll patients who have metastatic melanoma that is refractory to treatment with an anti-PD-1 inhibitor in the metastatic setting. This study will also evaluate the safety, tolerability, and anti-tumor activity of tebentafusp (IMCgp100) monotherapy in patients with advanced non-uveal melanoma who progressed on prior PD-1 inhibitors approved for the treatment of advanced melanoma; patients with BRAF mutations must be refractory to approved BRAF-based therapy.

Read the detailed description

As of Amendment 9, a potential phase 2 portion of the study was to be opened after identification of the recommended phase 2 dose (RP2D) for Arm 5 (tebentafusp sc monotherapy). However, the phase 2 portion of the study was never initiated.

Being tested
Tebentafusp (IMCgp100)
Keywords
IMCgp100, gp100, metastatic cutaneous melanoma, checkpoint inhibitor, PD-1, PD-L1, CTLA-4, durvalumab, tremelimumab, Tebentafusp, Bispecific T cell receptor fusion protein, ImmTAC, Immune mobilizing monoclonal T cell receptor against cancer, Immunotherapy, mucosal melanoma, acral melanoma, tebentafusp (IMCgp100), Kimmtrak
Medical subject headings
Melanoma, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tebentafusp (IMCgp100)Drug

    soluble gp100-specific T cell receptor with anti-CD3 scFV

Study groups in NCT02535078
Study groupRoleWhat they receive
Phase 2: Tebentafusp SC MonotherapyExperimentalTebentafusp (IMCgp100) (single agent) subcutaneous (SC) injection
Receives: Drug: Tebentafusp (IMCgp100)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 2: Objective Response Rate (ORR)

    Measured: Up to ~2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2015 (estimated)
  2. Study startNov 2015
  3. Primary completion19 Jun 2023
  4. Study completion6 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02535078
Sponsor's protocol ID
IMCgp100-201
Status last verified
Jul 2024
First submitted
26 Aug 2015
Last updated
24 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Hamid O, Hassel JC, Shoushtari AN, Meier F, Bauer TM, Salama AKS, Kirkwood JM, Ascierto PA, Lorigan PC, Mauch C, Orloff M, Evans TRJ, Holland C, Edukulla R, Abedin SE, Middleton MR. Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study. J Immunother Cancer. 2023 Jun;11(6):e006747. doi: 10.1136/jitc-2023-006747.

    PubMed 37286303

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tebentafusp (IMCgp100) in people with Malignant Melanoma, run by Immunocore Ltd at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 2: Objective Response Rate (ORR) (time frame: Up to ~2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02535078, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.

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