Relatlimab

Opdualag showed no difference from Opdivo alone in terms of risk of disease recurrence or death in adjuvant treatment of completely resected stage 3 and 4 melanoma, according to results published at the 2025 American Society of Clinical Oncology annual meeting. Despite its success in advanced melanoma, Bristol Myers Squibb’s fixed-dose PD-1/LAG-3 combo, Opdualag, failed to move the needle in resected skin cancer.After revealing in February that Opdualag failed as a postsurgery adjuvant treatment for patients with completely resected stage 3 and 4 melanoma, BMS has peeled back full results from the negative Relativity-098 trial at the 2025 American Society of Clinical Oncology annual meeting.At a minimum follow-up of 23.4 months, Opdualag—a combo of Opdivo and the LAG-3 antibody relatlimab—showed no difference from Opdivo alone in terms of patients' risk of disease recurrence or death. About 39% of patients in both arms of the trial had experienced recurrence or passed away.At the two-year mark, 62% of patients in the Opdualag arm remained alive without recurrence, versus 63.6% in the Opdivo group. The median recurrence-free survival time was not reached for the Opdualag arm, while it was 33.1 months for the control group.Treatment with Opdualag was associated with a higher rate of grade 3 or 4 treatment-related adverse events, 19%, compared with 8% for Opdivo alone. Two treatment-related deaths happened in the 547-patient Opdualag arm, compared with one case in the 546-subject Opdivo arm. The adjuvant melanoma flop again brings the utility of LAG-3 antibodies into question and draws attention to BMS’ somewhat controversial decision last year to push Opdivo and a higher dose of relatlimab into phase 3 testing in the all-important setting of first-line non-small cell lung cancer (NSCLC).But to BMS Chief Medical Officer Samit Hirawat, M.D., findings from a study in adjuvant melanoma have little bearing on the combo's promise in metastatic NSCLC.Relatlimab potentiates the immune system and the working of Opdivo in the environment when the tumor is present, attracting T cells to work for Opdivo, Hirawat explained.Relatively-098, meanwhile, was conducted in resected melanoma, where patients had no tumors present.In the metastatic setting, where the tumor is present, “we do see that patients who have a non-small cell lung cancer with expression of PD-1 greater than 1%, those are the patients that benefit,” Hirawat said.The BMS exec was referring to data from the phase 2 Relativity-104 trial, which didn’t impress in a first-line NSCLC all-comers population. But when sharing the data at last year’s European Society of Medical Oncology Congress, BMS pointed to improvements in nonsquamous patients whose PD-L1 expression was between 1% to 49% to justify its decision to launch the phase 3 Relativity1093 trial in that population. The study was later edited to include all PD-L1-positive patients after the company examined the PD-L1-high data further.  BMS’ decision was not very well received. Critics argued that the company was trying too hard to find a positive signal and, in the process, cutting the data too thin. The control arm in the phase 2 trial also appeared to have underperformed historical data, raising questions about the validity of the positive signals that BMS saw. Despite the latest adjuvant melanoma setback, “we remain pretty confident about conducting” the first-line NSCLC trial, Hirawat said.

STAFFORD, TX, USA and TUEBINGEN, Germany I May 31, 2025 I Immatics N.V. (NASDAQ: IMTX, “Immatics” or the “Company”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today announced the presentation of expanded data from the ongoing Phase 1b clinical trial evaluating IMA203 PRAME cell therapy in heavily pretreated patients with metastatic melanoma. The longer follow-up of patients demonstrates a consistent and favorable tolerability profile as well as durable responses with a confirmed ORR of 56%. In addition, the Company provided details from a Trial in Progress poster on SUPRAME, the ongoing Phase 3 clinical trial evaluating IMA203 in patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor. The data from the ongoing Phase 1b trial will be presented on Saturday, May 31, 2025, during an oral presentation by Martin Wermke, M.D. The Trial in Progress poster (TiP) will be presented at the conference on Monday, June 2, 2025, by Jason Luke, M.D., FACP, FASCO. The IMA203 slides, including the ASCO data and additional data, are accessible in the ‘ Events & Presentations ’ section of the Investor & Media section of the Company’s website. “Patients with advanced melanoma post-failure of checkpoint inhibition are left to face frequent and often rapid disease progression and limited long-term survival. These individuals are in urgent need of new treatments that deliver deeper and more durable responses,” said Cedrik Britten, M.D., Chief Medical Officer at Immatics. “We believe the data presented today emphasize the strength, durability and tangible therapeutic potential of our one-time infusion PRAME cell therapy, IMA203, in this patient population. These positive results reinforce our commitment to actively advance IMA203 through the ongoing Phase 3 SUPRAME trial to bring this PRAME therapy to the market as soon as possible.” “PRAME is a highly prevalent target that is expressed in more than 50 cancers. This, combined with the data presented at ASCO, further strengthens our position as the global leader in precision targeting of PRAME. We view our progress in melanoma as a critical step in our journey to building the broadest PRAME franchise with the most indications and modalities and delivering novel PRAME immunotherapies to cancer patients with high unmet medical needs,” said Harpreet Singh, Ph.D., Chief Executive Officer and Co-Founder at Immatics. Oral Presentation Summary – IMA203 Phase 1b Trial Patient Population: Heavily pretreated patients with metastatic melanoma As of April 7, 2025, 33 heavily pretreated patients with metastatic melanoma were administered a one-time infusion of IMA203 at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR T cells) in the Phase 1b dose expansion. The treated patient population consisted of cutaneous melanoma (n=14), uveal melanoma (n=16), mucosal melanoma (n=2) and melanoma of unknown primary (n=1). Patients had a median of 2 lines of prior systemic treatments. The subgroup of patients with cutaneous melanoma had a median of 2.5 lines of prior systemic treatments, thereof a median of 2 lines of prior immune checkpoint inhibitors. Safety: Favorable tolerability The safety population included 74 patients combined from the Phase 1a dose escalation and Phase 1b dose expansion across all dose levels and all tumor types. IMA203 has maintained a favorable tolerability profile. The most frequent treatment-emergent adverse events were anticipated cytopenias associated with lymphodepletion. Expected and manageable cytokine release syndrome (CRS) was mostly Grades 1 and 2, which is consistent with the mechanism of action (Grade 1: 37%, Grade 2: 47%, Grade 3: 11%, Grade 4: 0%). No patients experienced long-term CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred infrequently, was manageable and mostly mild (Grade 1: 5%, Grade 2: 4%, Grade 3: 4%, Grade 4: 0%). No IMA203-related Grade 5 events were observed. Tolerability in the Phase 1b melanoma subset was generally consistent with the full IMA203 tolerability profile. Anti-tumor activity and durability: Encouraging anti-tumor activity of IMA203 PRAME cell therapy, including durable responses up to >2.5 years with longer follow-up The PFS rate was 53% at six months and 27% at 12 months. The overall survival rate was 61% at 12 months. In addition, 42% (14/33) of patients had a deep response (≥50% tumor reduction) with a mPFS of 12.9 months. Translational analyses demonstrated that treatment with IMA203 resulted in the shrinkage of metastatic target lesions throughout the body. This included reductions in difficult-to-treat metastases, such as liver, lung, lymph node, abdomen/peritoneum, skin and others. Some individual lesions had a complete resolution (-100%). All patients (n=3) who had a best overall response of progressive disease according to RECIST 1.1 experienced shrinkage of individual lesions. The positive Phase 1b data and high PRAME prevalence (~90-95% in melanoma) reinforce the potential of IMA203, which is currently being evaluated in the ongoing SUPRAME Phase 3 trial in previously treated advanced or metastatic cutaneous melanoma, as well as the continued Phase 1b expansion into uveal melanoma. Trial-in-Progress Poster Summary – IMA203 SUPRAME Phase 3 Trial Based on the positive clinical data and supported by the FDA RMAT designation 4 , Immatics advanced its PRAME cell therapy, IMA203, into the randomized-controlled Phase 3 SUPRAME trial ( NCT06743126 ). SUPRAME is a prospective, multicenter, open-label, randomized, actively controlled Phase 3 clinical trial evaluating the efficacy, safety and tolerability of IMA203 vs. investigator’s choice in ~360 patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor. Patient eligibility is determined by protocol inclusion/exclusion criteria, including HLA screening. If patients are HLA-A*02:01 positive and meet the eligibility criteria, they will undergo leukapheresis and be randomized 1:1. Patients in the IMA203 arm will undergo lymphodepletion with cyclophosphamide (500 mg/m 2 x 4 days) and fludarabine (30 mg/m 2 x 4 days), subsequent infusion of 1-10 x10 9 IMA203 PRAME-directed TCR T cells, followed by low-dose IL-2 5 (subcutaneous). Patients in the control arm will receive either nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (in the US), or chemotherapy based on investigator’s choice. The primary endpoint is blinded independent central review (“BICR”)-assessed (RECIST 1.1) PFS. Secondary endpoints include OS, ORR, safety and patient-reported outcomes about quality of life. The expected median PFS in this post-checkpoint inhibitor patient population 6 is 2-3 months, and the IMA203 Phase 1b data presented today at ASCO indicate a continued median PFS of ≥6 months. SUPRAME is planned to be conducted in more than 50 sites in North America and Europe. Patient enrollment and randomization for the trial was initiated in early 2025 and is expected to be completed in 2026. A pre-specified interim data analysis will be triggered upon the occurrence of a defined number of events for PFS (progressive disease or death) 7 , anticipated to occur after approximately 200 patients. Immatics aims to submit a Biologics License Application (BLA) to the FDA in 1Q 2027 for full approval. About PRAME PRAME is a target expressed in more than 50 cancers. Immatics is the global leader in precision targeting of PRAME and has the broadest PRAME franchise with the most PRAME indications and modalities. The Immatics PRAME franchise currently includes three product candidates, two therapeutic modalities and a combination therapy that target PRAME: IMA203 PRAME cell therapy, IMA203CD8 PRAME cell therapy (GEN2), IMA402 PRAME bispecific, IMA203 in combination with Moderna’s PRAME adaptive immune modulating therapy. About IMA203 PRAME Cell Therapy IMA203 is a PRAME-directed TCR T-cell therapy engineered to recognize an intracellular PRAME-derived peptide presented by HLA-A*02:01 on the cell surface and initiate a potent and specific anti-tumor response. IMA203 PRAME cell therapy is currently being evaluated in a registration-enabling randomized controlled Phase 3 trial, “SUPRAME,” in patients with unresectable or metastatic cutaneous melanoma who have disease progression on or after treatment with at least one checkpoint inhibitor. In parallel, the Phase 1b clinical trial in patients with PRAME cancers is ongoing with a focus on uveal melanoma. About Immatics Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer. Immatics intends to use its website www.immatics.com as a means of disclosing material non-public information. For regular updates you can also follow us on LinkedIn and Instagram . 1 Melanoma efficacy population includes n=3 patients with other melanoma subtypes (n=2 mucosal melanoma, n=1 melanoma of unknown primary; data can be found in the IMA203 slides). 2 cORR excludes 1 uveal melanoma patient with ongoing unconfirmed PR. 3 NR, not reached PD: progressive disease; BL: baseline; PR: partial response; (c)ORR: (confirmed) objective response rate; DCR: disease control rate at week 6; mDOR: median duration of response; mFU: median follow-up; mPFS: median progression-free survival; mOS: median overall survival 4 Includes all benefits of Breakthrough Therapy Designation. 5 1m IU daily days 1-5 and twice daily days 6-10, total dose is approx. only 5% of the overall dose for high-dose IL-2 given typically with TIL therapy (Sarnaik et al. 2021 Journal of Clinical Oncology). 6 Ascierto et al., 2023, Diab et al., 2024. 7 Centrally assessed by BICR using RECIST v1.1. SOURCE: Immatics