On May 31, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that KEYTRUDA (pembrolizumab) plus Trodelvy (sacituzumab govitecan-hziy) reduced the risk of disease progression or death by 35% (HR=0.65, p<0.001) versus KEYTRUDA plus chemotherapy for the first-line treatment of patients with PD-L1+ (Combined Positive Score [CPS] ≥10) inoperable (unresectable) locally advanced or metastatic triple-negative breast cancer (TNBC), as determined by an FDA-approved test. KEYTRUDA, when given in combination with Gilead’s TROP2 antibody-drug conjugate (ADC) Trodelvy, resulted in a median progression-free survival (PFS) of 11.2 months versus 7.8 months when KEYTRUDA was given in combination with chemotherapy (Press release, Merck & Co, MAY 31, 2025, View Source [SID1234653548]). These data from the pivotal Phase 3 ASCENT-04/KEYNOTE-D19 study will be presented today as a late-breaking oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #LBA109) and were selected for the official ASCO (Free ASCO Whitepaper) Press Program.

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"These results have the potential to be an important advancement for patients with PD-L1–positive metastatic triple-negative breast cancer, a population for whom first-line options remain limited," said Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04/KEYNOTE-D19 study. "By combining sacituzumab govitecan with pembrolizumab, we’re seeing meaningful gains in progression-free survival and a promising trend in overall survival—findings that could support a new frontline standard of care for this aggressive disease."

The safety profile of KEYTRUDA plus Trodelvy in this study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination. The two companies plan to share these results with regulatory authorities worldwide.

"We’re committed to building on the established role of KEYTRUDA as a foundational treatment for people with TNBC to provide new options in earlier lines of treatment, in the hope of improving outcomes for people living with this disease," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "These data support the addition of this TROP2-directed ADC to KEYTRUDA, demonstrating the potential to help people with TNBC and to give doctors another option to treat this disease."

A statistically significant and clinically meaningful improvement was observed with KEYTRUDA plus Trodelvy (n=221), showing a 35% reduction in the risk of disease progression or death (HR=0.65; p<0.001) in the intent-to-treat population compared to KEYTRUDA plus chemotherapy (n=222). The PFS benefit was generally consistent across key prespecified subgroups including age, curative treatment-free interval and geographic region.

A higher objective response rate (ORR) was observed for the KEYTRUDA plus Trodelvy combination (59.7% [95% CI, 52.9-66.3] versus 53.2% [95% CI, 46.4-59.9]), including 13% and 8% with a complete response, respectively, in the KEYTRUDA plus Trodelvy and KEYTRUDA plus chemotherapy arms. Notably, a substantially longer duration of response (DOR) was observed with KEYTRUDA plus Trodelvy (16.5 months [95% CI, 12.7-19.5] versus 9.2 months [95% CI, 7.6-11.3]). Encouraging trends in overall survival (OS) were also observed, but data are immature at the time of PFS primary analysis. Overall survival follow-up remains ongoing and will continue to be monitored as a key secondary endpoint.

Merck has a comprehensive clinical development program in various subtypes of breast cancer including evaluating KEYTRUDA in combination with investigational TROP2 ADCs (trophoblast cell-surface antigen-directed antibody-drug conjugates) in metastatic and early-stage cancers. The company has four ongoing Phase 3 studies in breast cancer, with two being in metastatic disease.

In the U.S. and Europe, KEYTRUDA has two approved indications in TNBC: for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; and in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

As announced, data spanning more than 25 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting.

About the ASCENT-04/KEYNOTE-D19 Study

In 2021, Merck entered a collaboration with Gilead to investigate KEYTRUDA plus Trodelvy in the Phase 3 ASCENT-04/KEYNOTE-D19 open-label, global trial (ClinicalTrials.gov, NCT05382286). The primary endpoint is PFS as determined by BICR using RECIST v1.1. Secondary endpoints include OS, ORR, DOR, time to onset of response (TTR), patient-reported outcomes (PROs) and safety. The study enrolled 443 patients who were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously [IV] on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg IV on Day 1 of a 21-day cycle) or chemotherapy plus pembrolizumab. The chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity and at this time patients randomized to chemotherapy were allowed to crossover and receive sacituzumab govitecan upon disease progression.

About triple-negative breast cancer (TNBC)

Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA1 mutation.

On May 31, 2025 Mythic Therapeutics, a clinical-stage biotechnology company developing next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported updated data from its Phase 1 KisMET-01 study evaluating its investigational cMET-targeting ADC candidate, MYTX-011, in patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC), in a poster at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Mythic Therapeutics, MAY 31, 2025, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-compelling-efficacy-data-from-its-phase-1-kismet-01-study-supporting-best-in-class-potential-of-novel-cmet-adc-mytx-011-in-non-small-cell-lung-cancer-asco-2025 [SID1234653549]). MYTX-011 is a novel ADC engineered with pH-dependent binding to more precisely deliver anti-tumor payload across a range of cMET expression levels, with the goal of reducing toxicity and expanding the number of patients who can benefit from ADC therapy.

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"We are highly encouraged by these early efficacy data demonstrating meaningful anti-tumor activity which underscore how our differentiated pH-dependent design may help unlock the full promise of ADCs to reshape cancer treatment and expand patient reach, regardless of histology and molecular subtype," said George Eliades, Ph.D., President and Chief Executive Officer at Mythic Therapeutics. "Together with a manageable tolerability profile, these findings support the potential of MYTX-011 to establish a new standard of care for pretreated NSCLC patients in second- and later-line settings, where effective treatment options remain extremely limited. We look forward to evaluating MYTX-011 in Part 2 of the study and plan to present updated expansion cohort data at an upcoming medical conference."

Data presented were from 66 patients treated at efficacious dose levels (≥4.0 mg/kg) administered once every three weeks (Q3W) in Part 1 of the dose escalation portion of the study. Patients had a median of three, and up to 10, prior lines of therapy with nearly half (45%) receiving prior taxane treatments. Preliminary results show:

Anti-tumor activity was consistent regardless of cMET expression levels, EGFR mutation status or prior taxane treatment.
In non-squamous, cMET+ tumors, the ORR was 39% in cMET high/intermediate (n=23) and 36% in cMET low tumors (n=11).
Responses were observed in patients with and without actionable genomic alterations, including a 50% ORR in patients with tumors containing both EGFR mutations and cMET high or intermediate expression.
Overall, responses were durable, with observed durations of up to 8.9 months and ongoing; the majority of patients with responses remain on treatment.
Disease control rate (DCR) was 80% at 12 weeks (n=24 of 30) and 52% at 24 weeks (n=14 of 27).
All four response-evaluable patients with squamous histology tumors and low cMET levels had clinical benefit; one partial response was observed and the three other patients had durable stable disease.
MTYX-011 demonstrated favorable pharmacokinetics (PK) and excellent stability. The overall safety profile of MYTX-011 was consistent with previously reported data, and no new safety signals were identified. The most common treatment-related adverse events (TRAEs) of any grade in 20% or more of patients included, blurred vision (47%), keratopathy (41%), keratitis (32%), nausea (29%), peripheral neuropathy (24%), fatigue (23%), and increased AST (21%). Grade 3 or higher TRAEs in 5% or more of patients included blurred vision (20%), keratopathy (18%), neutropenia (14%), and keratitis (11%). 11 of the 12 reports of neutropenia and 12 of the 16 cases of peripheral neuropathy occurred in patients treated at doses of 5.8 mg/kg or higher. Ocular AEs led to treatment discontinuation in four patients (6%), with three of the four patients receiving doses of 5.8 mg/kg or higher. Based on clinical data and favorable PK, a 5.0 mg/kg dose on a Q3W regimen with a 2-on, 1-off dose break schedule was selected as the recommended Phase 2 dose, which will be compared to a 4.0 mg/kg Q3W dose in Part 2 of the trial.

"The early data from the MYTX-011 study, showing compelling anti-tumor activity and durable responses in patients with lung cancer, together with a well-tolerated safety profile, are highly encouraging," said Rebecca Heist, M.D., MPH, Medical Oncologist, Massachusetts General Hospital, Cancer Center. "These findings suggest that MYTX-011 has the potential to become a promising new treatment option for a broad range of NSCLC patients, and we are eager to continue evaluating its efficacy and safety in the ongoing dose expansion phase of the study."

About KisMET-01

KisMET-01 (NCT05652868) is a multicenter, first-in-human Phase 1 study of MYTX-011 in patients with previously treated, locally advanced or metastatic NSCLC. The study is comprised of two parts: dose escalation (Part 1) in patients with NSCLC of any histology of cMET expression with cMET analyzed whenever tumor tissue is available, followed by dose expansion (Part 2) in cMET-positive (cMET+) patients selected by immunohistochemistry (Ventana SP44). cMET levels are defined as high (≥50% tumor cells with 3+ staining), intermediate (≥25% and <50% with 3+ staining), low (≥25% with 2+ staining, excluding high and intermediate), and ultra-low (≥75% excluding high, intermediate, and low).

About MYTX-011

MYTX-011 is an investigational cMET-targeting ADC, which leverages Mythic’s innovative FateControl technology. FateControl ADCs are pH engineered to unbind their target after internalization, intended to improve both tumor uptake and drug exposure for improved safety, tolerability and efficacy. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

On May 31, 2025 Xilio therapeutics presented its corporate presentation (Presentation, Xilio Therapeutics, MAY 31, 2025, View Source [SID1234653628]).

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On May 31, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported detailed analyses from the Phase 3 C-POST trial, which evaluated PD-1 inhibitor Libtayo (cemiplimab) in patients with high-risk cutaneous squamous cell carcinoma (CSCC) after surgery (Press release, Regeneron, MAY 31, 2025, View Source [SID1234653550]). The results, shared during an oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM), include additional data for the primary endpoint of disease-free survival (DFS) and the first presentation of key secondary endpoint outcomes.

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"While surgery and radiotherapy remain the cornerstones of treatment for high-risk cutaneous squamous cell carcinoma, there is a critical unmet need for systemic therapies to help prevent relapse and metastasis to ultimately drive better outcomes for patients," said Danny Rischin, M.D., M.B.B.S., F.R.A.C.P., Research Lead, Head and Neck Cancer and Cutaneous SCC, Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, and lead investigator of the trial. "The Phase 3 C-POST trial demonstrates that cemiplimab is a highly active therapy in high-risk CSCC, with clinically meaningful outcomes across primary and secondary endpoints and exceptionally low rates of locoregional and distant recurrence."

Results from the C-POST trial shared earlier this year established Libtayo as the first immunotherapy to show a statistically significant and clinically meaningful benefit in high-risk CSCC in the adjuvant setting. In contrast, negative results with another PD-1 are presented at ASCO (Free ASCO Whitepaper). The data with Libtayo at this year’s ASCO (Free ASCO Whitepaper) provide additional insights for the primary endpoint of DFS – defined as time from randomization to the first documented disease recurrence or death – as well as first results for the secondary endpoints of freedom from locoregional recurrence, freedom from distant recurrence and overall survival (OS).

With a median duration of follow-up of 24 months (range: 2-64 months), efficacy results for Libtayo compared to placebo, were as follows:

68% reduction in the risk of disease recurrence or death (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.20-0.51; p<0.0001), with median DFS not reached for Libtayo-treated patients (versus 49 months for placebo)
At two years, DFS was 87% with Libtayo versus 64% with placebo
80% reduction in the risk of locoregional recurrence (HR: 0.20; 95% CI: 0.09-0.40)
65% reduction in the risk of distant recurrence (HR: 0.35; 95% CI: 0.17-0.72)
Updated OS data from a recent data cut, with approximately six months of additional follow up after the primary analysis for DFS, suggest an emerging OS benefit for Libtayo (HR: 0.78; 95% CI: 0.39-1.56) versus placebo.

"These results show the continued promise of Libtayo in non-melanoma skin cancers," said Israel Lowy, M.D., Ph.D., Clinical Development Unit Head, Oncology, at Regeneron. "Libtayo is the first medicine to demonstrate a statistically significant benefit in patients who have high-risk features for recurrence after resection of cutaneous squamous cell carcinoma and has the potential to become a new standard of care in the adjuvant setting. We are working with global regulatory authorities to bring this new option to patients as quickly as possible."

Additionally, an exploratory analysis of the C-POST results showed similar rates of DFS regardless of PD-L1 expression level. Specifically, Libtayo reduced the risk of disease recurrence or death by 72% in tumors with PD-L1 ≥1% (HR: 0.28; 95% CI: 0.15-0.52; n=309) and by 68% in tumors with PD-L1 <1% (HR: 0.32; 95% CI: 0.12-0.86; n=85), compared to placebo.

Safety was assessed in 205 patients in the Libtayo arm and 204 patients in the placebo arm. Adverse events (AEs) of any grade occurred in 91% and 89% of patients in the Libtayo arm and the placebo arm, respectively. Grade ≥3 AEs occurred in 24% and 14% of patients in the Libtayo arm and the placebo arm, respectively. The most common AEs occurring in at least 10% of patients in the Libtayo arm were fatigue, pruritus, rash, diarrhea, arthralgia, hypothyroidism and maculo-paplar rash. The only grade ≥3 AE that occurred in more than 2% of patients in the Libtayo arm was hypertension. Treatment discontinuations due to AEs, regardless of attribution, occurred in 10% and 2% of patients in the Libtayo arm and the placebo arm, respectively. Two patients experienced an AE leading to death in each arm.

The potential use of Libtayo described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

Regulatory applications have been submitted for Libtayo in the treatment of adjuvant CSCC in the United States and European Union.

About the Phase 3 Trial
C-POST is one of several trials from Regeneron’s oncology portfolio and pipeline being shared at ASCO (Free ASCO Whitepaper).

C-POST was a randomized, placebo-controlled, double-blind, multicenter, global Phase 3 trial investigating Libtayo versus placebo as adjuvant treatment for patients with features associated with a high-risk of CSCC recurrence and who had completed surgery and post-operative radiation therapy. Trial participants were at high risk of recurrence due to nodal features (extracapsular extension or ≥3 involved lymph nodes) and/or non-nodal features (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥1 additional poor prognostic features).

The trial enrolled 415 patients who were randomized to receive either Libtayo (n=209) or placebo (n=206) for up to 48 weeks. For the first 12 weeks, Libtayo 350 mg or placebo was administered intravenously every three weeks, followed by Libtayo 700 mg or placebo administered intravenously every six weeks for 36 weeks.

On May 30, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported results from the dose confirmation portion of the Phase 2/3 waveLINE-003 study evaluating zilovertamab vedotin in combination with standard of care rituximab and gemcitabine-oxaliplatin (R-GemOx) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Merck & Co, MAY 30, 2025, View Source [SID1234653521]). Zilovertamab vedotin is an investigational, potential first-in-class antibody drug conjugate (ADC) that targets receptor tyrosine kinase-like orphan receptor 1 (ROR1). At a pre-planned analysis, zilovertamab vedotin 1.75 mg/kg in combination with R-GemOx achieved a 56.3% objective response rate (ORR) in patients with relapsed or refractory DLBCL (n=16), with eight complete responses (CR) and one partial response (PR). These data are being presented for the first time today during an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #7005).

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"Patients with relapsed or refractory diffuse large B-cell lymphoma continue to experience poor outcomes and an unmet need remains to help provide these patients with additional options to treat their cancer," said Dr. Philippe Armand, the study’s principal investigator, Dana-Farber Cancer Institute. "These data from the Phase 2 portion of the waveLINE-003 trial are encouraging for patients and support further research in the relapsed/refractory setting in a larger patient population."

"In the Phase 2 portion of the waveLINE-003 trial, the 1.75 mg/kg dose of zilovertamab vedotin with rituximab, gemcitabine and oxaliplatin demonstrated a promising response rate, complete response rate and manageable safety profile in combination with standard of care," said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. "The Phase 3 portion of this trial is already enrolling, and as we continue to advance our research of this investigational ROR1-directed ADC, these promising results amplify our belief in the potential of zilovertamab vedotin to treat multiple hematologic malignancies."

Zilovertamab vedotin is currently being evaluated in patients with previously untreated DLBCL in the Phase 3 waveLINE-010 study (NCT06717347) and in the Phase 2 waveLINE-007 study (NCT05406401). Additionally, we recently initiated the Phase 2 waveLINE-011 study (NCT06890884), which is a randomized, open-label clinical trial evaluating zilovertamab vedotin plus rituximab and cyclophosphamide, doxorubicin and prednisone (R-CHP) versus polatuzumab vedotin with R-CHP for the treatment of patients with DLBCL. The trial is estimated to enroll 594 patients and the primary endpoint is CR rate at end of treatment, with secondary endpoints of progression-free survival (PFS), overall survival (OS), event-free survival, duration of CR and safety. Global recruitment of the waveLINE-011 study has begun, with patients now enrolling.

As announced, data spanning more than 25 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting.

Study design and additional data from waveLINE-003
WaveLINE-003 is a Phase 2/3 randomized, multicenter, open-label, dose confirmation and expansion clinical trial (ClinicalTrials.gov, NCT05139017) designed to assess the safety and efficacy of zilovertamab vedotin in combination with standard of care options for the treatment of relapsed or refractory DLBCL after one or more lines of therapy. This study is divided into two parts: dose confirmation (part 1) and efficacy expansion (part 2) and enrolled adult participants with confirmed relapsed or refractory DLBCL after one or more lines of therapy and an Eastern Cooperative Oncology Group performance status of 0-2. In Part 1, primary endpoints were safety and recommended Phase 2 dose (RP2D). Secondary endpoints were ORR, duration of response (DOR) per Lugano 2014 response criteria by blinded independent central review and OS. Part 1 of the trial enrolled 40 patients (as of the August 1, 2024 data cutoff) to receive either:

Zilovertamab vedotin (1.5 mg/kg intravenously [IV]) plus rituximab (375 mg/m2 IV), gemcitabine (1000 mg/m2 IV) and oxaliplatin (100 mg/m2 IV), given every three weeks (Q3W) up to six cycles (n=17), or
Zilovertamab vedotin (1.75 mg/kg IV) plus R-GemOx Q3W up to six cycles (n=16), or
Zilovertamab vedotin (2.0 mg/kg IV) plus R-GemOx Q3W up to six cycles (n=7).
Treatment-related adverse events (TRAEs) were reported in 98% of patients (n=40). Grade ≥3 TRAEs occurred in 63% of patients (n=25). At the 1.5 mg/kg dose of zilovertamab vedotin plus R-GemOx, four patients completed treatment, eight discontinued due to progression and one withdrew, with four patients receiving ongoing treatment at data cut-off. At the 1.75 mg/kg dose, eight patients completed treatment, seven discontinued due to progression and one patient discontinued due to physician decision. In the 2.0 mg/kg dose cohort, three patients completed treatment, three patients discontinued treatment due to adverse events (AEs) (treatment-related sepsis and respiratory failure), and one patient withdrew due to physician decision. One patient died after discontinuing treatment due to treatment-related sepsis. The most common AEs were diarrhea, nausea, anemia and platelet count decrease, while the most common Grade ≥3 AEs were neutropenia, neutrophil count decrease, platelet count decrease and anemia.

Seven dose-limiting toxicities occurred across all participants. At the 1.5 mg/kg dose of zilovertamab vedotin plus R-GemOx, one participant had Grade 4 febrile neutropenia. At the 1.75 mg/kg dose, one participant experienced Grade 3 alanine aminotransferase increased and one patient had intestinal obstruction. At the 2.0 mg/kg dose, participants had Grade 3 diarrhea, Grade 4 neutrophil count decrease and Grade 4 thrombocytopenia (one patient each), and one patient experienced both Grade 3 febrile neutropenia and Grade 4 neutrophil count decrease.

The median follow-up for all participants was 9.8 months. At a median follow-up of 18.1 months (range, 2.4 to 23.3 months) in patients receiving the 1.5 mg/kg dose of zilovertamab vedotin (n=15), ORR was 26.7% (3 CR [20.0%], 1 PR [6.7%]) and median DOR was 14.4 months (95% CI, not reached [NR]-NR). At a median follow-up of 9.9 months (range, 4.0 to 30.0 months) for patients receiving the 1.75 mg/kg dose (n=16), ORR was 56.3% (8 CR [50.0%], 1 PR [6.3%]) and median DOR was 8.7 months (95% CI, 2.3-NR). At a median follow-up of 9.3 months (range, 6.0 to 10.0 months) for patients receiving the 2.0 mg/kg dose (n=7), the ORR was 57.1% (3 CR [42.9%], 1 PR [14.3%]) and median DOR was not reached (95% CI, 4.1-NR). Based on these results and accompanying safety data, the recommended Phase 2 dose of zilovertamab vedotin was determined to be 1.75 mg/kg when used with R-GemOx.

About diffuse large B-cell lymphoma
Lymphoma is cancer beginning in the lymphatic system – the network of organs, vessels and tissues that protects the body from infection. There are many subtypes of lymphoma, which is often categorized into two main types – Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma, the most common form of NHL, is derived from white blood cells that grow rapidly and uncontrollably, enlarging the lymph nodes and often migrating to other parts of the body. DLBCL accounts for approximately 25-30% of all NHLs worldwide. In the U.S., it is estimated that approximately 25,000 patients are diagnosed with DLBCL each year. The five-year relative survival rate for DLBCL is 60-70%.

About zilovertamab vedotin (MK-2140)
Zilovertamab vedotin is an investigational, potential first-in-class ADC that targets ROR1. ROR1 is a transmembrane protein that is overexpressed in multiple hematologic malignancies. Merck is committed to research with zilovertamab vedotin across B-cell malignancies and has established a robust program of clinical trials under the name waveLINE. In addition to waveLINE-003, the waveLINE program includes a Phase 3 study in patients with previously untreated DLBCL (waveLINE-010, NCT06717347), a Phase 2 study in patients with select B-cell lymphomas (waveLINE-006, NCT05458297), a Phase 2 study in patients with germinal center B-cell-like DLBCL (waveLINE-011, NCT06890884) and a Phase 2 study in patients with previously untreated DLBCL (waveLINE-007, NCT05406401).