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  • Pembrolizumab Plus Lenvatinib Shows Encouraging Efficacy in Uveal Melanoma | Targeted Oncology

    Pembrolizumab Plus Lenvatinib Shows Encouraging Efficacy in Uveal Melanoma | Targeted Oncology

    The combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) elicited promising progression-free survival (PFS) outcomes in patients with uveal melanoma who were both HLA-A*02:01–negative and –positive with a manageable safety profile, according to findings from the phase 2 PLUME trial (NCT05282901) presented at the 2025 ESMO Congress.1

    The study met its primary end point in both patient cohorts, with an observed PFS rate of 31.8% at 27 weeks (95% CI, 13.9%-54.9%) in patients who were HLA-A*02:01–negative and naïve for treatment with tebentafusp (Kimtrak). In patients who were HLA-A*02:01–positive and were pretreated with tebentafusp, the PFS rate at 27 weeks was 60.7% (95% CI, 40.6%-78.5%).

    “It was observed in phase 3 studies of tebentafusp2 that treatments administered after tebentafusp might display improved activity compared [with] historical data,” said Manuel Rodrigues, MD, medical oncologist at Institut Curie and presenter of the PLUME data.1

    The combination of lenvatinib and pembrolizumab “showed encouraging activity, especially in patients previously treated with tebentafusp, suggesting potential synergy between these treatments,” Rodrigues added.

    Regarding safety, the overall profile was consistent with prior trials involving pembrolizumab and lenvatinib. There were no treatment-related deaths. With lenvatinib, 76% of patients held the dose, 26% had dose reductions, and 4% discontinued. With pembrolizumab, 22% of patients held the dose and 4% discontinued.

    The most common any-grade treatment-related adverse events were fatigue (81.8% in the tebentafusp-naive cohort vs 69% in the pretreated cohort), hypertension (77.3% vs 69%), diarrhea (45.5% vs 65.5%), hypothyroidism (45.5% vs 65.5%), arthralgia (40.9% vs 58.6%), cytolytic hepatitis (40.9% vs 58.6%), mucositis (45.5% vs 41.4%), dysphonia (31.8% vs 44.8%), and abdominal pain (27.3% vs 44.8%).

    While the findings were promising, Rodrigues urged caution when interpreting the results, due to the small sample size and single-arm design. Rodrigues noted that biomarker analyses and real-world comparisons were ongoing to further refine patient selection.

    What Was the Design of the PLUME Study?

    PLUME was an academic, monocentric, single-arm phase 2 trial conducted at the Institut Curie in Paris, France.A total of 51 patients who were naïve to immune checkpoint inhibitors were enrolled and split into 2 cohorts by HLA-A*02:01–negative (n = 22) and –positive/pretreated with tebentafusp (n = 29).

    Treatment consisted of pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles and lenvatinib 20 mg orally daily until progression. Chest, abdomen, and pelvic CT scans and liver MRIs were mandatory every 9 weeks. The primary end point was 27-week PFS (after 9 cycles).

    What Was the Rationale for the PLUME Study?

    As Rodrigues explained in his presentation, uveal melanoma has a unique biology to melanoma of the skin, with one-third of patients developing metastases and over 90% of those patients developing liver metastases. The current median overall survival (OS)is about 20 months.

    Tebentafusp, a bispecific TCR–anti-CD3 fusion protein targeting gp100, was the first therapy to improve OS in patients with metastatic uveal melanoma; however, the benefit is limited to patients who are HLA-A*02:01–positive, which is about 45% of patients. Further, checkpoint inhibitors like pembrolizumab have shown limited efficacy due to low mutational burden and an immunosuppressive microenvironment.

    The rationale of adding lenvatinib lies in its VEGFR/FGRF blockade that can normalize vasculature, reduce tumor-associated macrophages, and enhance T-cell infiltration. The combination of lenvatinib and pembrolizumab has shown promise in endometrial and renal cancers, where the combination has outperformed monotherapy.

    DISCLOSURES: Rodrigues declared personal financial interests with Immunocore, GSK, AstraZeneca, and Abbvie; institutional financial interests with Johnson & Johnson, Merck, and Daiichi-Sankyo; and nonfinancial interests with Merck, which provided product samples for the PLUME trial.

    REFERENCES:

    1. Rodrigues M. PLUME: A single-arm phase II trial of pembrolizumab plus lenvatinib in metastatic uveal melanoma (mUM). Presented at: 2025 ESMO Congress; October 17–20, 2025; Berlin, German. Abstract LBA58.

    2. Nathan P, Hassel JC, Rutkowski P, et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. doi: 10.1056/NEJMoa2103485.

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  • Iran says it is no longer bound by ‘restrictions’ on nuke plan – Dawn

    1. Iran says it is no longer bound by ‘restrictions’ on nuke plan  Dawn
    2. Iran announces official end to 10-year-old nuclear agreement  The Guardian
    3. Iran says restrictions on nuclear programme ‘terminated’ as deal expires  Al Jazeera
    4. Five…

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  • Itch.io down? How to fix ‘Error 1200’

    Itch.io down? How to fix ‘Error 1200’

    Published on: Oct 19, 2025 08:31 am IST

    Itch.io is currently down for hundreds of users across the United States. Many users reported ‘Error 1200.’

    Itch.io is currently down for hundreds of users across the United States. Many…

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  • Pakistan’s Asim Munir continues warmongering, rattles nuclear sabre second time in two months – Firstpost

    Pakistan’s Asim Munir continues warmongering, rattles nuclear sabre second time in two months – Firstpost

    Pakistan’s Army Chief Field Marshal Asim Munir once again resorted to war-mongering tactics against India after he said that Islamabad would “respond much beyond the expectations of the initiators”

    Pakistan’s Army Chief Field Marshal
    Asim…

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  • Einstein’s overlooked idea could explain how the Universe really began

    Einstein’s overlooked idea could explain how the Universe really began

    How did the universe come into existence, and what early processes shaped everything that followed? A new study published in Physical Review Research takes aim at this fundamental question. Scientists from Spain and Italy have introduced a model…

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  • Einstein’s overlooked idea could explain how the Universe really began

    Einstein’s overlooked idea could explain how the Universe really began

    How did the universe come into existence, and what early processes shaped everything that followed? A new study published in Physical Review Research takes aim at this fundamental question. Scientists from Spain and Italy have introduced a model…

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  • Nintendo, Capcom stepping up efforts to bring game worlds to big screen

    Nintendo, Capcom stepping up efforts to bring game worlds to big screen

    OSAKA – Major Japanese game developers Nintendo Co. and Capcom Co. are stepping up efforts to bring their iconic game characters and worlds to the big screen.

    Nintendo plans to release the animated film “The Super Mario Galaxy Movie” in…

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  • Calm returns to Chaman after ceasefire extension – Dawn

    1. Calm returns to Chaman after ceasefire extension  Dawn
    2. Afghan transit trade halted as border tensions rise  The Express Tribune
    3. Torkham, Chaman border crossings remain closed for trade due to ‘security situation’  Daily Times
    4. Taliban-Pakistan…

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  • IHC office objects to KP CM’s plea for meeting Imran – Dawn

    1. IHC office objects to KP CM’s plea for meeting Imran  Dawn
    2. Shehbaz assures cooperation as Afridi takes K-P helm  The Express Tribune
    3. Politics over peace  The News International
    4. Imran Khan grants authority to CM Afridi for cabinet formation  samaa…

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  • Afghanistan, Pakistan agree to immediate ceasefire after talks in Doha | Conflict News

    Afghanistan, Pakistan agree to immediate ceasefire after talks in Doha | Conflict News

    South Asian neighbours also agreed to hold follow-up meetings in coming days to ensure peace deal’s implementation.

    Afghanistan and Pakistan have agreed to an…

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