# US 2025/0367285 A1 · Methods of treating melanoma using tebentafusp and immune checkpoint inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0367285 A1 - Document ID: US20250367285A1 - Status: Published application - Kind: A1 - Application number: 18/871,402 - Filed: 2023-06-02 - Published: 2025-12-04 - Earliest claimed: 2022-06-03 - Applicants: Immunocore Limited; Astrazeneca AB - Inventors: Shaad ABDULLAH; Christina COUGHLIN; Ashok GUPTA; Shannon MORRIS - Web page: https://patentgrep.com/patent/US20250367285A1 ## CPC - A61K 39/39558: {against tumor tissues, cells, antigens} - A61P 17/00: Drugs for dermatological disorders - A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex} - C07K 16/2818: {against CD28 or CD152} - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - C07K 2317/622: Single chain antibody (scFv) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention relates to the treatment of melanoma in a patient, where the method includes administering to a patient who has or is suspected of having melanoma a therapeutically effective amount of tebentafusp; and a therapeutically effective amount of an immune checkpoint inhibitor. In particular, patients may have metastatic melanoma that is refractory to treatment with an anti-PD(L)1 inhibitor in the metastatic setting or where the patient's melanoma is relapsed following treatment with an anti-PD(L)1 inhibitor. ## Claims ### Claim 1 A method of treating melanoma in a patient, comprising: administering to a patient who has or is suspected of having melanoma: a therapeutically effective amount of tebentafusp; and a therapeutically effective amount of a first immune checkpoint inhibitor. ### Claim 2 A method of treating melanoma in a patient, comprising: administering to a patient who is refractory to or relapsed following a prior checkpoint inhibitor treatment: a therapeutically effective amount of tebentafusp; and a therapeutically effective amount of a first immune checkpoint inhibitor. ### Claim 3 (depends on 2) The method of claim 2, wherein the prior immune checkpoint inhibitor treatment comprises an inhibitor of PD(L)1, CTLA-4, or a combination thereof. ### Claim 4 (depends on 1, 2, 3) The method of any one of claims 1-3, further comprising administering a second immune checkpoint inhibitor. ### Claim 5 (depends on 1, 2, 3, 4) The method of any one of claims 1-4, wherein the first immune checkpoint inhibitor or the second immune checkpoint inhibitor is an inhibitor of PD(L)1. ### Claim 6 (depends on 5) The method of claim 5, wherein the inhibitor is a monoclonal antibody that binds PD(L)1. ### Claim 7 (depends on 6) The method of claim 6, wherein the monoclonal antibody that binds PD(L)1 is selected from: durvalumab, atezolizumab, BMS-936559, avelumab, pembrolizumab, nivolumab, dostarlimab, and cemiplimap. ### Claim 8 (depends on 7) The method of claim 7, wherein the monoclonal antibody that bind PD(L)1 is durvalumab. ### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8) The method of any one of claims 1-8, wherein the first immune checkpoint inhibitor and/or the second immune checkpoint inhibitor is an inhibitor of CTLA-4. ### Claim 10 (depends on 9) The method of claim 9, wherein the inhibitor is a monoclonal antibody that binds CTLA-4. ### Claim 11 (depends on 10) The method of claim 10, wherein the monoclonal antibody that binds CTLA-4 is selected from: tremelimumab, ipilimumab, quavonlimab, zalifrelimab, GIGA-564, CBT-509, and AGEN1181. ### Claim 12 (depends on 11) The method of claim 11, wherein the monoclonal antibody that binds CTLA-4 is tremelimumab. ### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) The method of any one of claims 1-12, wherein the melanoma is cutaneous melanoma. ### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The method of any one of claims 1-13, wherein the cutaneous melanoma is metastatic cutaneous melanoma. ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14) The method of any one of claims 1-14, wherein the melanoma is refractory or resistant. ### Claim 16 (depends on 15) The method of claim 15, wherein the patient was previously treated with an inhibitor of PD(L)1. ### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The method of any one of claims 1-16, wherein the patient has a BRAF mutation. ### Claim 18 (depends on 17) The method of claim 17, wherein the patient was previously treated with an approved BRAF-based therapy. ### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18) The method of any one of claims 1-18, wherein the patient is HLA-A2-positive. ### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19) The method of any one of claims 1-19, wherein the tebentafusp and the first immune checkpoint inhibitor are administered separately. ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The method of any one of claims 1-20, wherein the tebentafusp is administered weekly. ### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21) The method of any one of claims 1-21, wherein the first immune checkpoint inhibitor is administered once every four weeks. ### Claim 23 (depends on 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22) The method of any one of claims 4-22, wherein the second immune checkpoint inhibitor is administered once every four weeks. ### Claim 24 (depends on 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The method of any one of claims 4-23, wherein the first immune checkpoint inhibitor and the second immune checkpoint inhibitor are administered concurrently. ### Claim 25 (depends on 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The method of any one of claims 4-23, wherein the first immune checkpoint inhibitor and the second immune checkpoint inhibitor are administered separately. ### Claim 26 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25) The method of any one of claims 1-25, wherein the first immune checkpoint inhibitor, the second immune checkpoint inhibitor, or both, are first administered about 15 days after the first administration of the tebentafusp. ### Claim 27 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26) The method of any one of claims 1-26, wherein the tebentafusp is administered at a dose ranging from about 10 mcg to about 68 mcg. ### Claim 28 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26) The method of any one of claims 1-26, wherein the tebentafusp is administered at a dose ranging from about 10 mcg to about 50 mcg. ### Claim 29 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26) The method of any one of claims 1-26, wherein the tebentafusp is administered at a dose ranging from about 68 mcg to about 200 mcg. ### Claim 30 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29) The method of any one of claims 1-29, wherein the first immune checkpoint inhibitor, the second immune checkpoint inhibitor, or both, are administered at a dose ranging from about 1 mg/kg to about 20 mg/kg. ### Claim 31 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29) The method of any one of claims 1-29, wherein the first immune checkpoint inhibitor, the second immune checkpoint inhibitor, or both, are administered at a dose ranging from about 0.5 mg/kg to about 10 mg/kg. ### Claim 32 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29) The method of any one of claims 1-29, wherein the first immune checkpoint inhibitor, the second immune checkpoint inhibitor, or both, are administered at a dose ranging from about 0.5 mg/kg to about 1 mg/kg. ### Claim 33 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18) The method of any one of claims 1-18, wherein the first immune checkpoint inhibitor is durvalumab. ### Claim 34 (depends on 33) The method of claim 33, wherein the tebentafusp is administered at a dose ranging from about 10 mcg to about 68 mcg and the durvalumab is administered at a dose ranging from about 1 mg/kg to about 20 mg/kg. ### Claim 35 (depends on 33, 34) The method of claims 33 or 34, wherein the tebentafusp is administered about once weekly. ### Claim 36 (depends on 33, 34, 35) The method of any one of claims 33-35, wherein the durvalumab is administered about once every four weeks. ### Claim 37 (depends on 36) The method of claim 36, wherein the durvalumab is first administered about 15 days after the first administration of the tebentafusp. ### Claim 38 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18) The method of any one of claims 1-18, wherein the first immune checkpoint inhibitor is tremelimumab. ### Claim 39 (depends on 38) The method of claim 38, wherein the tebentafusp is administered at a dose ranging from about 10 mcg to about 50 mcg and the tremelimumab is administered at a dose ranging from about 0.5 mg/kg to about 10 mg/kg. ### Claim 40 (depends on 38, 39) The method of claims 38 or 39, wherein the tebentafusp is administered about once weekly. ### Claim 41 (depends on 38, 39, 40) The method of any one of claims 38-40, wherein the tremelimumab is administered about once every four weeks. ### Claim 42 (depends on 41) The method of claim 41, wherein the tremelimumab is first administered about 15 days after the first administration of the tebentafusp. ### Claim 43 (depends on 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18) The method of any one of claims 4-18, wherein the first immune checkpoint inhibitor is durvalumab and the second immune checkpoint is tremelimumab. ### Claim 44 (depends on 43) The method of claim 43, wherein the tebentafusp is administered at a dose ranging from about 10 mcg to about 50 mcg, the durvalumab is administered at a dose ranging from about 1 mg/kg to about 20 mg/kg, and the tremelimumab is administered at a dose ranging from about 0.5 mg/kg to about 1 mg/kg. ### Claim 45 (depends on 43, 44) The method of claim 43 or 44, wherein the tebentafusp is administered about once weekly. ### Claim 46 (depends on 43, 44, 45) The method of any one of claims 43-45, wherein the durvalumab is administered about once every four weeks. ### Claim 47 (depends on 46) The method of claim 46, wherein the durvalumab is first administered about 15 days after the first administration of the tebentafusp. ### Claim 48 (depends on 43, 44, 45, 46, 47) The method of any one of claims 43-47, wherein the tremelimumab is administered about once every four weeks. ### Claim 49 (depends on 48) The method of claim 48, wherein the tremelimumab is first administered about 15 days after the first administration of the tebentafusp. ### Claim 50 (depends on 43, 44, 45, 46, 47, 48, 49) The method of any one of claims 43-49, wherein the first immune checkpoint inhibitor and the second immune checkpoint inhibitor are administered concurrently. ### Claim 51 (depends on 43, 44, 45, 46, 47, 48, 49) The method of any one of claims 43-49, wherein the first immune checkpoint inhibitor and the second immune checkpoint inhibitor are administered separately. ### Claim 52 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51) The method of any one of claims 1-51, wherein tebentafusp is administered via intravenous infusion, subcutaneous infusion, intramuscular infusion, enteral administration, inhalation, or intranasal. ### Claim 53 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52) The method of any one of claims 1-52, wherein the first immune checkpoint inhibitor, the second immune checkpoint inhibitor, or both are administered via intravenous infusion, subcutaneous infusion, intramuscular infusion, enteral administration, inhalation, or intranasal. ### Claim 54 A method of treating metastatic cutaneous melanoma in a patient, comprising: administering: tebentafusp at a dose ranging from about 10 mcg to about 68 mcg; and a PD(L)1 inhibitor at a therapeutically effective amount, wherein the tebentafusp is administered about once weekly, wherein the PD(L)1 inhibitor is administered about once every four weeks, and wherein the PD(L)1 inhibitor is first administered about 15 days after the first administration of the tebentafusp. ### Claim 55 (depends on 54) The method of claim 54, wherein the PD(L)1 inhibitor is a monoclonal antibody that binds PD(L)1. ### Claim 56 (depends on 55) The method of claim 55, wherein the monoclonal antibody that binds PD(L)1 is selected from: durvalumab, atezolizumab, BMS-936559, and Avelumab. ### Claim 57 (depends on 56) The method of claim 56, wherein the PD(L)1 inhibitor is durvalumab. ### Claim 58 A method of treating metastatic cutaneous melanoma in a patient, comprising: administering: tebentafusp at a dose ranging from about 10 mcg to about 68 mcg; and durvalumab at a dose ranging from about 1 mg/kg to about 20 mg/kg, wherein the tebentafusp is administered about once weekly, wherein the durvalumab is administered about once every four weeks, and wherein the durvalumab is first administered about 15 days after the first administration of the tebentafusp. ### Claim 59 A method of treating metastatic cutaneous melanoma in a patient, comprising: administering: tebentafusp at a dose ranging from about 10 mcg to about 50 mcg; and a CTLA-4 inhibitor at a therapeutically effective amount, wherein the tebentafusp is administered about once weekly, wherein the CTLA-4 inhibitor is administered about once every four weeks, and wherein the CTLA-4 inhibitor is first administered about 15 days after the first administration of the tebentafusp. ### Claim 60 (depends on 59) The method of claim 59, wherein the CTLA-4 inhibitor is a monoclonal antibody that binds CTLA-4. ### Claim 61 (depends on 60) The method of claim 60, wherein the monoclonal antibody that binds CTLA-4 is selected from: tremelimumab, ipilimumab, quavonlimab, zalifrelimab, GIGA-564, CBT-509, and AGEN1181. ### Claim 62 (depends on 61) The method of claim 61, wherein the CTLA-4 inhibitor is tremelimumab. ### Claim 63 A method of treating metastatic cutaneous melanoma in a patient, comprising: administering: tebentafusp at a dose ranging from about 10 mcg to about 50 mcg; and tremelimumab at a dose ranging from about 0.5 mg/kg to about 10 mg/kg, wherein the tebentafusp is administered about once weekly, wherein the tremelimumab is administered about once every four weeks, and wherein the tremelimumab is first administered about 15 days after the first administration of the tebentafusp. ### Claim 64 A method of treating metastatic cutaneous melanoma in a patient, comprising: administering: tebentafusp at a dose ranging from about 10 mcg to about 50 mcg; a PD(L)1 inhibitor at a therapeutically effective amount; and a CTLA-4 inhibitor at a therapeutically effective amount, wherein the tebentafusp is administered about once weekly, wherein the PD(L)1 inhibitor is administered about once every four weeks, wherein the CTLA-4 inhibitor is administered about once every four weeks, and wherein the PD(L)1 inhibitor and the CTLA-4 inhibitor are first administered about 15 days after the first administration of the tebentafusp. ### Claim 65 (depends on 64) The method of claim 64, wherein the inhibitor is a monoclonal antibody that binds PD(L)1. ### Claim 66 (depends on 65) The method of claim 65, wherein the monoclonal antibody that binds PD(L)1 is selected from: durvalumab, atezolizumab, BMS-936559, and Avelumab. ### Claim 67 (depends on 66) The method of claim 66, wherein the PD(L)1 inhibitor is durvalumab. ### Claim 68 (depends on 64, 65, 66, 67) The method of any one of claims 64-67, wherein the inhibitor is a monoclonal antibody that binds CTLA-4. ### Claim 69 (depends on 68) The method of claim 68, wherein the monoclonal antibody that binds CTLA-4 is selected from: tremelimumab, ipilimumab, quavonlimab, zalifrelimab, GIGA-564, CBT-509, and AGEN1181. ### Claim 70 (depends on 69) The method of claim 69, wherein the CTLA-4 inhibitor is tremelimumab. ### Claim 71 A method of treating metastatic cutaneous melanoma in a patient, comprising: administering: tebentafusp at a dose ranging from about 10 mcg to about 68 mcg; durvalumab at a dose ranging from about 1 mg/kg to about 20 mg/kg; and tremelimumab at a dose ranging from about 0.5 mg/kg to about 10 mg/kg, wherein the tebentafusp is administered about once weekly, wherein the durvalumab is administered about once every four weeks, wherein the tremelimumab is administered about once every four weeks, and wherein the durvalumab and the tremelimumab are first administered about 15 days after the first administration of the tebentafusp.