Cycle on Aug 17, 2026

I will start by listing the open threads and watches for this topic, as well as reading the current notes to understand the landscape and see if any of our existing watches or threads need updating.

I will read the current notes for this topic to understand what has already been documented and to identify any potential overlaps or areas for updates.

Let's see what's happening. The current date is August 17, 2026. Let's search for recent news in science, health, space, energy, and medicine to see what's new. Let's start with a broad search on recent health and science news, and specifically check some of the watches that might be close to firing or have recent updates, or any other major news in the last week. Wait, let's look at the current date: August 17, 2026. Let's see: - "Launch of NASA's Nancy Grace Roman Space Telescope" scheduled for August 30, 2026. - "CARDIO-TTRansform full dataset presentation at ESC Congress 2026" - ESC Congress is scheduled for late August 2026 (usually late August, e.g., Aug 28 - Aug 31). - What about any other major recent FDA decisions, clinical trials, outbreaks, or science breakthroughs? Let's do a web search with `sort="recent"` and `freshness="week"`.I will search for recent major science and health news from the past week to see what significant events, drug approvals, trial readouts, or policy shifts have occurred.

Let's analyze the search results: 1. **Zenbexus (iberdomide)** was approved by the FDA on August 11, 2026. Wait! We have a prior note/watch on this? Let's see: we have a prior finding `bms-zenbexus-iberdomide-multiple-myeloma-approval` titled "Bristol Myers Squibb's Zenbexus Wins Historic First-in-Class FDA Approval in Multiple Myeloma" updated on August 16, 2026. Wait, let's look at the threads/watches: - `019feddb-a316-76c7-beeb-a199a4b65d4b`: "Replimune Phase 3 IGNYTE-3 confirmatory trial results for Tudriqev in melanoma" - wait, Tudriqev (RP1) was approved recently (accelerated approval on August 6, 2026). The watch is for the Phase 3 IGNYTE-3 confirmatory trial results (expected late 2027). So it hasn't fired yet. - `019ff2fd-92ac-748d-8d1e-294157933221`: "FDA regulatory decision on Belite Bio's tinlarebant NDA in Stargardt disease" (Feb 12, 2027). - `019ffd4e-c975-720d-903a-e8d16d07cfe6`: "ITM NDA resubmission for ITM-11 in GEP-NETs" (resubmission after August 2026 CRL). - `01a0079b-2493-7ec5-b616-680631330a60`: "Definium Phase 3 Panorama trial readout of DT120 in GAD" (expected September 2026). - `01a0079b-680b-7359-8e07-478358915d9c`: "FDA Advisory Committee meeting on GRAIL's Galleri MCED test" (September 23, 2026). - `01a0079b-a362-7b6f-8bb4-d053c71ea597`: "FDA regulatory decision on BMS's mezigdomide NDA in multiple myeloma" (May 13, 2027). Wait, let's look at the other search results. What is this: "Summit, Akeso’s China approval celebration cut short as survival benefit degrades. Ivonescimab notched its third approval in China last week, but the label update has tempered expectations for the Summit Therapeutics/Akeso drug, showing that progression-free survival declines over time. But as part of the approval, the NMPA posted some new data on the drug’s label showing degradation of progression free survival (PFS) in the Phase 3 HARMONi-6 trial..." Wait, let's search for this! This looks extremely interesting and very recent (published 8 hours ago, so August 17, 2026). Let's do a search on "ivonescimab" and "China" or "Akeso" or "Summit" or "HARMONi-6" or "survival benefit degrades".

Let's fetch the Endpoints or BioSpace article to see what exactly is the updated PFS analysis / degradation of PFS in the HARMONi-6 trial that came with the China approval label update. Wait, let's look at the Endpoints article URL or the BioSpace article: BioSpace: `https://www.biospace.com/drug-development/summit-akesos-china-approval-celebration-cut-short-as-survival-benefit-degrades` Let's fetch this.

Let's search for "Endpoints" "ivonescimab" to see if we can get a bit more detail on what the "unwelcome surprise" was on the label. Let's do a search on `site:endpoints.news ivonescimab` to get the exact numbers if possible, or search for "HARMONi-6" "hazard ratio" or "PFS" "tislelizumab" in the past week.

Let's search for "endpoints.news" "ivonescimab" "PFS" or "survival benefit degrades" to see what exactly the "smaller benefit with longer follow-up" was. Wait, let's search for the exact PFS numbers or hazard ratio that was on the label of ivonescimab in China, or what the Leerink analyst wrote. Let's search: `Leerink "ivonescimab" "HARMONi-6"` or `"HARMONi-6" "label" PFS`. This will help us find the exact numbers and details.

Ah, let's search for "Buried within the Chinese regulators' label for ivonescimab is a disclosure" to see if we can get the text of the Endpoints article or the exact numbers. Let's do a web search for: `"Buried within the Chinese regulators' label for ivonescimab is a disclosure" OR "PFS" "HARMONi-6" "label"` to get the exact numbers.

Let's fetch the Endpoints News article: `https://endpoints.news/summit-akesos-ivonescimab-shows-smaller-benefit-with-longer-follow-up-in-china/` to read the exact details of the label disclosure and why the analysts are concerned. This is critical for our latest research cycle!

Ah, it seems the fetch returned a very short preview because it is paywalled or requires a login. No problem, let's search for some other articles, blog posts, or tweets that discuss the exact numbers from the label of HARMONi-6. Let's search: `"HARMONi-6" "median PFS" "label" OR "endpoints"` or `"HARMONi-6" "hazard ratio" label` or `"ivonescimab" "HARMONi-6" "label" PFS`. This will help us find the exact numbers and the "unwelcome surprise".

Let's search for some other terms: `Akeso "HARMONi-6" "hazard ratio" label` or `Akeso "HARMONi-6" label update` or `Akeso "HARMONi-6" label PFS`. Let's try to find if there is a newer PFS hazard ratio reported on the label. Wait! Let's search on Twitter or Google for the updated PFS hazard ratio or PFS median from the label. Let's search: `"HARMONi-6" label "hazard ratio" OR "HR" OR "PFS" "tislelizumab"` or `"HARMONi-6" PFS "0.60" OR "0.6"` or `"HARMONi-6" PFS "0.7"` or `"HARMONi-6" PFS "0.8"`. Let's see what comes up.

Let's do a search on: `"median PFS" "tislelizumab" "ivonescimab" "label"` to see if we can locate any posts or articles discussing the specific numbers on the Chinese label. Wait! Let's search: `"HARMONi-6" "PFS" label "hazard ratio"` or `"Akeso" "ivonescimab" "label" "PFS" "months"` or `"ivonescimab" "label" "PFS" "months"`. This can help us find the updated figures. Let's see what we get.

Aha! Let's look at the Endpoints snippet: "With about seven months of additional patient follow-up, ivonescimab produced a 28% reduction in the risk of disease progression or death, compared to a 40%..." Wait, let's search for more details from this Endpoints article. Let's do a search on: `"With about seven months of additional patient follow-up, ivonescimab produced a 28% reduction in the risk of disease progression or death"` or similar keywords to see if we can find the exact text or a discussion of this. This is extremely specific and excellent primary evidence. Let's search: `"seven months of additional patient follow-up" "ivonescimab"` or `"28% reduction" "ivonescimab" "PFS"`. Let's see.

Let's do a search on `"seven months of additional patient follow-up, ivonescimab produced a 28% reduction"` (or similar phrases) using wildcard or fewer terms to see if we can find more snippets of the article. Wait, let's look at the first snippet again: "Patients who received ivonescimab plus chemotherapy had a median PFS of 12.48 months, compared to 8.31 months for those who only got chemo. Previously, the ..." Wait! Is it comparing to tislelizumab plus chemo or just chemo? Wait, the HARMONi-6 trial was ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy. Let's see. Wait, what is the other trial? Let's check `HARMONi-A` or `HARMONi-2`. Wait! The snippet says: "Patients who received ivonescimab plus chemotherapy had a median PFS of 12.48 months, compared to 8.31 months for those who only got chemo." Wait, let's check if that was for EGFR-mutant NSCLC (which is HARMONi-A) or if it's indeed for squamous NSCLC (HARMONi-6). Let's search for: `"12.48 months" "ivonescimab"` or `"8.31 months" "ivonescimab"`. This will help us identify exactly which trial or indication this refers to.

Ah! The web search budget is spent. We have got some very good information. Let's analyze what we have: 1. **Ivonescimab (PD-1/VEGF bispecific antibody)** co-developed by Akeso and Summit Therapeutics. - On August 12, 2026, China's National Medical Products Administration (NMPA) approved its third lung cancer indication: ivonescimab in combination with chemotherapy for the first-line treatment of advanced squamous non-small cell lung cancer (sq-NSCLC). This approval was based on the Phase 3 HARMONi-6 (AK112-306) trial conducted in China. - The HARMONi-6 trial previously reported an interim PFS hazard ratio of 0.60 (95% CI: 0.46-0.78, P<0.0001), with a median PFS of 11.1 months versus 6.9 months for the control arm (tislelizumab + chemotherapy). - At the 2026 ASCO Annual Meeting Plenary Session (May 31, 2026), Dr. Shun Lu presented interim overall survival (OS) data showing median OS of 27.89 months for ivonescimab + chemo versus 23.69 months for tislelizumab + chemo (HR=0.66, P=0.0017). - **The Unwelcome Surprise:** Buried within the newly approved Chinese label is an updated disclosure. With about seven months of additional patient follow-up, the progression-free survival (PFS) benefit of ivonescimab over the comparator degraded. Instead of the initial 40% reduction in the risk of disease progression or death (HR of 0.60), the longer-term follow-up showed only a 28% reduction in risk (which corresponds to a hazard ratio of 0.72). - This "degradation" of progression-free survival over time has tempered analyst expectations and increased pessimism (e.g., from Leerink Partners) regarding ivonescimab's global prospects, specifically the ongoing global Phase 3 HARMONi-3 trial which is expected to read out its PFS analysis in the second half of 2026. Leerink notes that the FDA's bar for accelerated approval based on PFS in first-line NSCLC is high, and if the benefit degrades over time, securing accelerated approval is less likely, potentially delaying the U.S. launch from late 2027 to late 2029 (for squamous NSCLC) and late 2030 (for non-squamous NSCLC). - Summit's shares fell over 4% to $13.35 on Friday, August 14, 2026, following the Leerink note. Wait, let's look at the other events in this cycle. Let's see if we have any existing watches that have fired: - Let's look at our watches: 1. `019f490e-b47d-7dea-817e-56ffbad19c83`: CARDIO-TTRansform full dataset presentation at ESC Congress 2026. It is scheduled for late August 2026 (the current date is August 17, 2026, so it hasn't fired yet). 2. `019e9f1e-f092-7114-960b-1c3b5c994320`: Moderna Phase 3 mRNA-1018 bird flu vaccine trial readout. (No news of readout yet). 3. `019fb013-39c2-71d8-932b-66e49c963e6a`: Launch of NASA's Nancy Grace Roman Space Telescope. Scheduled for August 30, 2026. 4. Is there any other watch that has fired? Wait, what about the Replimune RP1 (Tudriqev) watch? - `019feddb-a316-76c7-beeb-a199a4b65d4b`: Replimune Phase 3 IGNYTE-3 confirmatory trial results for Tudriqev in melanoma. (Expected late 2027, so not fired). - Let's check if there is an existing note/finding for Replimune RP1. Yes, `replimune-rp1-melanoma-fda-advisory-committee` ("FDA Advisory Committee Backs Replimune's RP1 Efficacy in Advanced Melanoma", updated Aug 17, 2026) and `replimune-tudriqev-melanoma-fda-approval` ("FDA Grants Accelerated Approval to Replimune's TUDRIQEV (RP1) in Advanced Melanoma", updated Aug 15, 2026). Wait, let's see what is new. On August 12, 2026, *The Cancer Letter* published an episode/article discussing the Replimune RP1 approval ("What happened at FDA? Replimune approval raises questions" / "Amid political outcry, advisors accept weak data and give sponsor a chance to complete phase III trial"). The Cancer Letter discusses the controversy surrounding the accelerated approval of Replimune's RP1 (Tudriqev) in advanced melanoma. Wait! Let's read the prior findings or existing notes. We have: - `replimune-rp1-melanoma-fda-advisory-committee`: "FDA Advisory Committee Backs Replimune's RP1 Efficacy in Advanced Melanoma" - `replimune-tudriqev-melanoma-fda-approval`: "FDA Grants Accelerated Approval to Replimune's TUDRIQEV (RP1) in Advanced Melanoma" - `replimune-rp1-melanoma-fda-review`: "FDA Advisory Committee Backs Replimune's Twice-Rejected RP1 in Advanced Melanoma" Wait, these are already notes. Is there a new story we can write or update? Let's look at the "What happened at FDA? Replimune approval raises questions" and the "The Cancer Letter" podcast from August 12, 2026. Wait, let's see if we can update `replimune-tudriqev-melanoma-fda-approval` or `replimune-rp1-melanoma-fda-advisory-committee` to include the discussion of the "fog" and the debate around the systemic (abscopal) effect of intratumoral injections, the single-arm trial design, and the historical lack of control arms. Wait, let's write a note on the ivonescimab development first. Is there an existing note on ivonescimab? Let's check the existing notes list: - `innovent-cldn182-adc-gastric-cancer-phase3`: "World’s First CLDN18.2 ADC Submits NDA Following Phase 3 Gastric Cancer Win" - `tolebrutinib-eu-approval-fda-regulatory-divergence`: "Tolebrutinib Wins EU Approval as First nrSPMS Disability-Targeting Therapy..." Wait, there is NO existing note specifically on ivonescimab's PFS degradation or the HARMONi-6 trial! Oh wait, let's check the watches. There is an ongoing watch: `019e99fb-8b38-7220-afca-dbbf935aa64e`: "Global Phase 3 trial readouts for ivonescimab (HARMONi studies)". Wait, is there any other note? No, so we can write a fresh note on ivonescimab! Let's coin a stable slug like `summit-akeso-ivonescimab-harmoni-trials`. Let's carefully structure the note on ivonescimab: Title: `Summit and Akeso's Ivonescimab Faces Long-Term Efficacy Questions as China Label Reveals PFS Degradation` Slug: `summit-akeso-ivonescimab-harmoni-trials` Wait, let's read the guidelines for writing a note: - Carry 1-2 REPRESENTATIVE VERBATIM QUOTES, copied exactly, each kept with the link it came from. - Name and link the actual thing. - Interpret what it means. - Slug should be stable and track the subject. - No YAML frontmatter. The title is the first `# ` heading. Let's draft the ivonescimab note: # Summit and Akeso's Ivonescimab Faces Long-Term Efficacy Questions as China Label Reveals PFS Degradation On August 12, 2026, China's National Medical Products Administration (NMPA) approved the supplemental New Drug Application (sNDA) for ivonescimab (a PD-1/VEGF bispecific antibody co-developed by Akeso and Summit Therapeutics) in combination with chemotherapy for the first-line treatment of advanced squamous non-small cell lung cancer (sq-NSCLC). While this marks the third lung cancer approval for ivonescimab in China, the regulatory milestone was overshadowed by newly disclosed long-term data on the drug's label. Buried within the NMPA-approved label is an updated analysis from the Phase III HARMONi-6 trial showing that the drug's progression-free survival (PFS) benefit degrades over time with longer patient follow-up. In the initial interim analysis, ivonescimab plus chemotherapy demonstrated a 40% reduction in the risk of disease progression or death compared to tislelizumab plus chemotherapy (hazard ratio of 0.60; 95% CI: 0.46-0.78; P<0.0001). However, with approximately seven months of additional patient follow-up, the PFS benefit was reduced to 28% (a hazard ratio of 0.72). This degradation of efficacy has sparked pessimism among analysts, notably Leerink Partners, who are concerned that the ongoing global Phase III HARMONi-3 trial—intended to support an accelerated approval in the United States—may fail to show a substantial or durable PFS benefit. Consequently, analysts now expect a delayed U.S. launch of ivonescimab, pushing the projected timeline for squamous NSCLC from late 2027 to late 2029, and non-squamous NSCLC to late 2030. Following the disclosure, Summit's stock fell over 4% to close at $13.35 on August 14, 2026. ## Quotes > "With about seven months of additional patient follow-up, ivonescimab produced a 28% reduction in the risk of disease progression or death, compared to a 40%..." — [Summit and Akeso's PD-1xVEGF bispecific got a new approval in China. It came with an unwelcome surprise](https://endpoints.news/summit-akesos-ivonescimab-shows-smaller-benefit-with-longer-follow-up-in-china/) > "But as part of the approval, the NMPA posted some new data on the drug’s label showing degradation of progression free survival (PFS) in the Phase 3 HARMONi-6 trial that underpinned the regulatory clearance. The update spurred 'increased pessimism' from Leerink Partners, as Summit works to confirm the benefit of ivonescimab in global clinical trials to secure an FDA approval." — [Summit, Akeso’s China approval celebration cut short as survival benefit degrades](https://www.biospace.com/drug-development/summit-akesos-china-approval-celebration-cut-short-as-survival-benefit-degrades) ## Sources - [Summit and Akeso's PD-1xVEGF bispecific got a new approval in China. It came with an unwelcome surprise](https://endpoints.news/summit-akesos-ivonescimab-shows-smaller-benefit-with-longer-follow-up-in-china/) — Endpoints News report on the label disclosure and analyst reactions. - [Summit, Akeso’s China approval celebration cut short as survival benefit degrades](https://www.biospace.com/drug-development/summit-akesos-china-approval-celebration-cut-short-as-survival-benefit-degrades) — BioSpace coverage of the NMPA approval and Leerink Partners' updated projections. - [Ivonescimab Plus Chemotherapy Approved for First-Line Squamous NSCLC; HARMONi-6 Establishes New Gold Standard in Lung Cancer Treatment](https://www.prnewswire.com/news-releases/ivonescimab-plus-chemotherapy-approved-for-first-line-squamous-nsclc-harmoni-6-establishes-new-gold-standard-in-lung-cancer-treatment-302849685.html) — Akeso's press release detailing the NMPA approval and the trial's primary findings. *** Wait, let's also look at the Replimune RP1 (Tudriqev) controversy. Let's see if we should update an existing note or write a new one. Wait, let's look at the existing notes on Replimune: - `replimune-rp1-melanoma-fda-advisory-committee`: "FDA Advisory Committee Backs Replimune's RP1 Efficacy in Advanced Melanoma" (updated Aug 17, 2026) - `replimune-tudriqev-melanoma-fda-approval`: "FDA Grants Accelerated Approval to Replimune's TUDRIQEV (RP1) in Advanced Melanoma" (updated Aug 15, 2026) - `replimune-rp1-melanoma-fda-review`: "FDA Advisory Committee Backs Replimune's Twice-Rejected RP1 in Advanced Melanoma" (updated Aug 14, 2026) Wait, let's look at `replimune-rp1-melanoma-fda-advisory-committee` or `replimune-tudriqev-melanoma-fda-approval`. Let's update `replimune-tudriqev-melanoma-fda-approval` to incorporate the discussion from *The Cancer Letter* podcast published on August 12, 2026, which highlights the regulatory "fog" and the controversy surrounding the accelerated approval of an intratumoral injection based on a small single-arm trial. Wait, let's look at the current body of `replimune-tudriqev-melanoma-fda-approval` if possible, but we don't have its full text. Let's write an update to `replimune-tudriqev-melanoma-fda-approval` or `replimune-rp1-melanoma-fda-advisory-committee`. Wait! The instruction says: "If a prior finding has a genuine update (a development, a reversal, a new data point), reuse its slug to revise it rather than writing a near-duplicate." Let's update `replimune-rp1-melanoma-fda-advisory-committee` to include the post-approval oncology community debate and the insights from *The Cancer Letter* podcast, which directly followed the FDA's accelerated approval of Tudriqev on August 6, 2026. Wait, the podcast was published on August 12, 2026, and discusses the "fog" of FDA's decision-making and why the oncology community remains highly skeptical of single-arm trials for intratumoral injections due to the lack of proven systemic (abscopal) effects. Let's write the note for `replimune-rp1-melanoma-fda-advisory-committee` with the title: # FDA Advisory Committee Backs Replimune's RP1 Efficacy in Advanced Melanoma Amid Deepening Regulatory Questions Let's write a very thorough update that incorporates the August 12, 2026 discussion. Wait, let's draft the body: On August 6, 2026, the FDA granted accelerated approval to Replimune Group's Tudriqev (vusolimogene oderparepvec / RP1) in combination with nivolumab for advanced melanoma patients progressing on prior anti-PD-1 therapy. This regulatory milestone followed a 10-to-3 vote in favor of the drug by the Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) on July 30, 2026. However, the decision has sparked intense debate and confusion within the oncology community, with leading experts questioning the FDA’s consistency and the clinical trial design that underpinned the approval. The controversy centers on the fact that RP1 is an intratumoral injection (a genetically modified herpes simplex virus). Historically, intratumoral injections are known to cause local regression of the injected lesion, but rarely demonstrate a true systemic ("abscopal") effect. Because the approval was based on a small, single-arm trial with no comparative or synthetic control arm, and extremely "messy" patient-level data, many experts argue that a systemic benefit remains unproven. During the advisory committee, even biostatisticians and clinicians who voted "yes" expressed severe reservations, noting that the data was highly confounding and did not definitively establish a clinically meaningful benefit. Furthermore, the approval has highlighted a perceived lack of predictability in the FDA’s decision-making process under the current leadership of Commissioner Marty Makary and CBER. Under previous leadership, such applications would have faced a far more rigorous review by the Oncologic Drugs Advisory Committee (ODAC), where single-arm data of this nature would have struggled to secure support. The current environment has left many industry observers in "the fog" regarding the agency's regulatory standards. ## Quotes > "So my yes was pretty close to a no. And what I really want to do is abstain because I don't know the answer... But don't take that as a, yes, this is convincing data. Okay? Yes, I can evaluate." — [Janet Wittes, CTGTAC

I will now write the research note for the new findings regarding Summit and Akeso's ivonescimab, detailing the newly disclosed long-term data on its Chinese label showing a degradation of its progression-free survival (PFS) benefit over time, and how this has impacted global development expectations.

I will write the updated note for `replimune-rp1-melanoma-fda-advisory-committee` to capture the deepening regulatory questions and the oncology community's debate over the accelerated approval of Tudriqev (RP1).

I will register a new watch to monitor the upcoming PFS readout of the global Phase III HARMONi-3 trial of ivonescimab in first-line NSCLC, expected in the second half of 2026. This is a critical forward-looking tripwire that will determine if the long-term efficacy degradation observed in China's HARMONi-6 is replicated globally.

I will now finish this research cycle as all findings have been written and registered.

I have successfully completed the research cycle for this topic. Here is a summary of the findings and actions taken: ### 1. **New Finding: Ivonescimab's Long-Term PFS Degradation** * **Durable Subject Slug**: `summit-akeso-ivonescimab-harmoni-trials` * **Summary**: On August 12, 2026, China's NMPA granted its third lung cancer approval for ivonescimab (PD-1/VEGF bispecific antibody) in combination with chemotherapy for first-line advanced squamous non-small cell lung cancer (sq-NSCLC), based on the Phase III HARMONi-6 trial. However, the approval came with a newly disclosed long-term analysis on the Chinese label showing that the drug's progression-free survival (PFS) benefit degrades over time. With about seven months of additional patient follow-up, the PFS risk reduction fell from the initially reported 40% (HR of 0.60) to 28% (HR of 0.72). * **Implications**: This degradation has fueled concern among analysts (e.g., Leerink Partners) that the ongoing global Phase III HARMONi-3 trial might fail to demonstrate a substantial or durable PFS benefit, potentially delaying the U.S. launch from late 2027 to late 2029 (for squamous NSCLC) and late 2030 (for non-squamous NSCLC). ### 2. **Updated Finding: Tudriqev (RP1) Regulatory Controversy** * **Durable Subject Slug**: `replimune-rp1-melanoma-fda-advisory-committee` * **Summary**: Incorporated post-approval oncology community debate and insights from *The Cancer Letter* podcast. Experts have highlighted deep skepticism regarding the FDA’s accelerated approval of Replimune's Tudriqev (RP1) on August 6, 2026. The drug was approved based on a small, single-arm trial with messy patient-level data. Because RP1 is an intratumoral injection, many experts remain skeptical of its systemic (abscopal) effect, arguing that the lack of a comparative or synthetic control arm leaves true systemic benefit unproven. The decision has left many observers in "the fog" regarding the FDA's regulatory standards under current leadership. ### 3. **Forward-Looking Watch Registered** * **Title**: `Summit/Akeso Phase III HARMONi-3 trial results of ivonescimab in first-line NSCLC` * **Type**: Tripwire (`one_shot`, expected by December 31, 2026). * **Focus**: Monitor if the global Phase III HARMONi-3 trial replicates the long-term PFS degradation observed in China's HARMONi-6 trial.