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

NCT02535078 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IMCgp100-201
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Malignant Melanoma

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

Outcome Measures

Primary Outcomes (1)

• Phase 2: Objective Response Rate (ORR)

  Up to ~2 years

Study Arms (1)

Phase 2: Tebentafusp SC Monotherapy

EXPERIMENTAL

Tebentafusp (IMCgp100) (single agent) subcutaneous (SC) injection

Drug: Tebentafusp (IMCgp100)

Interventions

Tebentafusp (IMCgp100) DRUG

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

Phase 2: Tebentafusp SC Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Immunocore Ltd: lead
• AstraZeneca: collaborator

Study Sites (4)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• 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.

  PMID: 37286303 DERIVED

MeSH Terms

Conditions

Melanoma; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

tebentafusp

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2015
• First Posted: August 28, 2015
• Study Start: November 1, 2015
• Primary Completion: June 19, 2023
• Study Completion: September 6, 2023
• Last Updated: July 24, 2024

Record last verified: 2024-07

Locations

US (4)