American Society of Clinical Oncology (ASCO) Annual Meeting | Chicago | 2026
- Badari Andukuri
- 3 hours ago
- 10 min read
Bristol Myers Squibb
Targeted Protein Degrader Mezigdomide Demonstrates Strong Efficacy in Heavily Pretreated Relapsed or Refractory Myeloma Patients
Bristol Myers Squibb reported encouraging findings showing that the CELMoD candidate Mezigdomide reduced the likelihood of disease progression or death by more than half compared with standard therapy in patients with relapsed or refractory multiple myeloma.
Data from the Phase 3 Successor-2 study highlight the potential of CELMoD-based treatments to significantly improve clinical outcomes in this patient population.
The company presented late-stage results from the Phase 3 Successor-2 trial evaluating Mezigdomide in combination with Carfilzomib and Dexamethasone, referred to as MeziKd, compared with Carfilzomib and Dexamethasone alone.
The combination regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, with a median duration of 18 months versus 8.3 months in the control arm. This corresponds to a 52 percent reduction in the risk of disease progression or death.
The benefits of MeziKd were consistent across multiple patient groups, including those receiving second- and third-line treatments and individuals with high-risk disease characteristics. The overall response rate was notably higher in the MeziKd arm at 80.2 percent compared to 53.4 percent with standard therapy. Additionally, complete response or better was achieved in 26.7 percent of patients receiving MeziKd, versus 8.9 percent in the comparator group. Median overall survival data remain immature at this stage.
The safety findings aligned with the established profile of Mezigdomide and the combination regimen.
About the Successor-2 Study
An increasing number of patients with multiple myeloma become resistant to Lenalidomide and anti-CD38 therapies early in their treatment course, creating a need for new therapeutic options. The Successor-2 trial was designed to address this gap.
This study is a randomized, open-label, multicenter Phase 2/3 trial assessing both efficacy and safety of Mezigdomide combined with Carfilzomib and Dexamethasone versus the standard combination alone in patients with relapsed or refractory multiple myeloma.
The primary endpoint for the Phase 3 portion is progression-free survival. Secondary measures include overall survival, response rates, duration of response, time to disease progression, time to subsequent therapy, minimal residual disease negativity, and patient-reported quality of life.
What is mezigdomide and what is mechanism of action of mezigdomide?
Mezigdomide is an orally administered CELMoD agent developed through Bristol Myers Squibb’s targeted protein degradation platform. It is engineered to rapidly and effectively degrade key transcription factors, including Ikaros and Aiolos, which play a role in multiple myeloma cell survival.
Preclinical findings indicate that Mezigdomide can enhance T cell activity and help restore immune function that has become ineffective. Ongoing Phase 3 trials, including Successor-1 and Successor-2, are evaluating Mezigdomide-based oral combinations against current standard treatments in relapsed or refractory multiple myeloma.
BeOne
BeOne Medicines Sets New Industry Standard for Long-Term CLL Management with Extended Zanubrutinib Results
BeOne Medicines has established a definitive benchmark for lasting disease control in chronic lymphocytic leukemia (CLL) following a 78-month analysis of its zanubrutinib program. This observation window stands as the longest ever recorded for a next-generation Bruton’s tyrosine kinase (BTK) inhibitor in this therapeutic area.
These updated findings confirm that zanubrutinib provides enduring clinical advantages that persist well beyond the initial phase of therapy. Furthermore, the combination of zanubrutinib with the novel BCL2 inhibitor sonrotoclax is achieving exceptionally rapid and deep rates of undetectable minimal residual disease (uMRD), offering a promising framework for time-limited CLL treatment regimens.
SEQUOIA Trial Update Confirms Sustained Long-Term Efficacy
The SEQUOIA investigation now represents the most comprehensive follow-up study for a next-generation BTK inhibitor in frontline CLL management. After a median observation period of 84.01 months (ranging from 0.0 to 101.5), zanubrutinib demonstrated superior performance compared to the traditional regimen of bendamustine and rituximab (BR) in individuals with previously untreated CLL/SLL.
Primary progression-free survival (PFS) metrics at the 78-month mark include:
Overall PFS: 71.8% for zanubrutinib compared to 31.0% for the BR group.
Unmutated IGHV Population: 70.4% with zanubrutinib versus 17.4% for those on BR.
Mutated IGHV Population: 81.8% for zanubrutinib compared to 45.1% for the BR group.
Data regarding disease control following initial progression also favored the zanubrutinib arm:
78-Month PFS2: 81.3% for zanubrutinib versus 74.4% for the BR regimen.
78-Month COVID-Adjusted PFS2: 84.7% for zanubrutinib against 76.4% for the BR group.
Among the 241 patients initially treated with zanubrutinib, 26 experienced progression; notably, half of those individuals utilized subsequent BCL2 inhibitor-based salvage options, and 69.2% remained free of progression after more than three additional years of monitoring. The time elapsed before requiring secondary treatment was also significantly improved for those on zanubrutinib. The safety profile remained aligned with previous findings, revealing no emerging concerns.
Real-World Evidence Highlights Clinical Edge in Diverse Populations
Three major real-world studies, aggregating data from over 250,000 patients, support the role of zanubrutinib as a best-in-class BTK inhibitor with consistent safety and efficacy profiles.
Medicare Database Review: Among 10,523 frontline CLL/SLL patients, those administered zanubrutinib experienced a statistically significant reduction in risks related to mortality, the necessity for next-line intervention, or treatment cessation when compared to individuals treated with ibrutinib or acalabrutinib
Komodo Database Assessment: In a study of 16,788 patients with treatment-naive CLL, zanubrutinib was linked to a more favorable duration before the next therapy requirement and improved overall survival
Retrospective Safety Analysis: A review of 233,362 newly diagnosed patients initiating BTK inhibitors showed the lowest one-year rate of atrial fibrillation among those treated with zanubrutinib (11%) compared to 13% for acalabrutinib and 16% for ibrutinib
Rapid, Deep Responses with Zanubrutinib and Sonrotoclax
A Phase I/1b study evaluating treatment-naive CLL/SLL patients, with a median follow-up of approximately 34 months, showed that the all-oral combination of zanubrutinib and sonrotoclax achieved unmatched rates and speed of undetectable minimal residual disease, even in high-risk patient subgroups.
Key efficacy metrics include:
Overall Response Rate (ORR): 100%.
Complete Response Rate: 59.5%.
Optimal uMRD4 Achievement: 98.8%.
TP53/del(17p) Population uMRD: 92.9% across two distinct dosage levels.
Median Time to uMRD4: 4.5 months.
What is the mechanism of action of zanubrutinib?
A precision-engineered, oral small molecule designed for total and sustained inhibition of Bruton's tyrosine kinase via optimized selectivity and bioavailability. With the most expansive global labeling of any BTK inhibitor, it remains the only agent in its category proven superior to a competitor in a Phase III trial. It has been utilized by over 290,000 patients in 80 markets.
What is the mechanism of action of Sonrotoclax?
A potent, next-generation BCL2 inhibitor characterized by a short half-life and the absence of drug accumulation. It is authorized in the U.S. and China for relapsed/refractory mantle cell lymphoma and holds specific approvals in China for previously treated CLL/SLL.
What is the mechanism of action of Tacabrutideg?
A potential first-in-class oral BTK degrader currently being evaluated in an extensive global program, including three Phase III trials for relapsed/refractory CLL. It utilizes a novel platform to break down both wildtype and mutated BTK proteins, effectively addressing resistance. It has received FDA Fast Track designation and EMA PRIME status for select indications.
Phase 3 HERIZON-GEA-01 trial show that substituting standard trastuzumab with the HER2-targeted bispecific antibody ZIIHERA, combined with chemotherapy, with or without the anti-PD-1 antibody TEVIMBRA, extends survival in previously untreated patients
Core Efficacy Metrics: Survival, Progression, and Response
The trial evaluated the clinical impact of Ziihera (zanidatamab)-based combinations against the standard control regimen (trastuzumab plus chemotherapy).
Median Overall Survival (mOS): Patients receiving the triple combination of Ziihera, Tevimbra(tislelizumab), and chemotherapy achieved a median overall survival of 26.4 months, demonstrating a statistically robust and clinically meaningful advantage. Those treated with Ziiheraand chemotherapy alone reached a median overall survival of 24.4 months, while the control group recorded 19.2 months.
Median Progression-Free Survival (mPFS): Progression-free survival was also notably extended in both Ziihera-based treatment arms, with a median duration of 12.4 months, indicating consistent disease control compared to the control regimen.
Median Duration of Response (mDoR): The durability of response further supported these findings. Patients treated with the triple combination experienced a median duration of response of 20.7 months. In comparison, Ziihera plus chemotherapy achieved 14.3 months, while the control arm showed a shorter duration of 8.3 months.
ASCO 2026 Presentation Highlights Efficacy Across Subgroups
Following a median observation period of 26 months, the combination of Ziihera,
Tevimbra, and chemotherapy produced meaningful extensions in both progression-free and overall survival for individuals with PD-L1-positive as well as PD-L1-negative malignancies when evaluated against the control group; these clinical outcomes showed strong alignment across both the tumor area positivity (TAP) and combined positive score (CPS) quantification methodologies.
Among individuals classified under the TAP <1% and TAP ≥1% thresholds, the 18-month progression-free survival rates reached 50.3% and 42.6%, respectively, while the corresponding 24-month overall survival rates were recorded at 63.7% and 53.5% within the triple-therapy cohort.
For the PD-L1-negative group (TAP <1%), median overall survival extended to 29.7 months with the Ziihera, Tevimbra, and chemotherapy protocol, compared to 15.8 months for those assigned to the control protocol. Conversely, for the PD-L1-positive group (TAP ≥1%), median overall survival reached 26.4 months using the ZIIHERA, TEVIMBRA, and chemotherapy protocol, versus 21.2 months within the standard-of-care cohort. These observations remained uniform irrespective of the specific PD-L1 testing system employed.
In the TAP <1% subset, the combination of Ziihera, Tevimbra, and chemotherapy demonstrated a median progression-free survival of 18.5 months compared to 7.9 months in the control cohort, whereas in the TAP ≥1% population, the median progression-free survival was 11.3 months versus 8.3 months in the comparative control arm.
SUN PHARMA
Unloxcyt Shows 50% Response and Durable Remissions in Locally Advanced Cutaneous Squamous Cell Carcinoma
Long-term follow-up from the CK-301-101 trial demonstrates that Unloxcyt (cosibelimab) provides sustained clinical benefits for patients with locally advanced cutaneous squamous cell carcinoma (laCSCC). The data, presented by Sun Pharma, highlights a favorable safety profile with notably low rates of severe immune-related toxicity.
Clinical Efficacy in laCSCC
The study involved 64 adults (median age 77) receiving at least one dose. This cohort’s demographics, primarily male, align with real-world clinical observations for this disease.
Treatment Duration: Patients received a median of 29 doses over approximately 60 weeks.
Objective Response Rate (ORR): 50% of the cohort responded to treatment.
Complete Response (CR): 27%
Partial Response (PR): 23%
Durability: At a median follow-up of 31 months, the median duration of response (DOR) remained unreached, indicating long-term disease control.
Safety and Tolerability Profile
The updated safety data remains consistent with earlier smaller-scale analyses and current labeling.
Immune-Related Adverse Events (irAEs): While roughly 33% of patients experienced an irAE, high-grade toxicity was rare.
Severity: Only one patient (less than 2%) reported a Grade 3 or higher treatment-related dermatologic event.
General Toxicity: Treatment-emergent adverse events (TEAEs) were frequent but manageable; notably, no fatalities were linked to the treatment.
With a 50% response rate and nearly 3 years of follow-up, Unloxcyt maintains a robust efficacy-to-safety ratio, characterized by deep, durable responses and minimal high-grade immune complications.
REGENERON
Lynozyfic (Linvoseltamab) Shows 100% Response and Rapid Deep Remissions in Second‑Line Systemic AL Amyloidosis
What is its mechanism of action of Lynozyfic (linvoseltamab) ?
Linvoseltamab is a human BCMA×CD3 bispecific antibody designed to link B‑cell maturation antigen (BCMA) on abnormal plasma cells with CD3 on T cells, activating the immune system to attack and eliminate the disease‑driving plasma cells. It is already used in specific settings for adults with relapsed or refractory multiple myeloma and is now being investigated as a fixed‑duration monotherapy in systemic AL amyloidosis beyond the first line of treatment.
By binding BCMA on clonal plasma cells and CD3 on cytotoxic T cells, linvoseltamab brings these cells into close proximity and triggers T‑cell activation, immune synapse formation and targeted killing of the abnormal plasma cells. This rapid depletion of plasma cells reduces the production of pathogenic light chains that form amyloid deposits, which is central to controlling systemic AL amyloidosis.
What is the efficacy of linvoseltamab in systemic AL amyloidosis (preliminary LINKER‑AL2 data)?
In the preliminary Phase 1/2 analysis of LINKER‑AL2, 20 adults with second‑line‑plus systemic AL amyloidosis received subcutaneous linvoseltamab at either 80 mg (n=7) or 240 mg (n=13), and 60% had previously received daratumumab‑containing regimens.
With a median follow‑up of 9.5 months (range 1.6–13.3 months), no dose‑limiting toxicities were observed at either dose.
All patients achieved a hematologic response.
At 80 mg, 100% (7/7) reached at least a very good partial response and 71% (5/7) achieved complete response.
At 240 mg, 100% (13/13) achieved complete response.
Among the 17 patients remaining on study at data cut‑off, no hematologic progression was reported, suggesting durable disease control within current follow‑up.
How fast does linvoseltamab work in AL amyloidosis?
Treatment with linvoseltamab led to rapid and deep reductions in involved free light chains, which normalized by day 15 across dose levels, indicating swift clearance of the pathogenic plasma cells. The median time to hematologic complete response was 47 days (range 7–240 days), showing that many patients can reach deep remissions within weeks.
What organ benefits have been observed so far?
In this early analysis, linvoseltamab was associated with meaningful organ signals in systemic AL amyloidosis. Among patients with kidney involvement, 73% (8 of 11) showed renal improvement, and among those with cardiac involvement, 50% (4 of 8) demonstrated biochemical improvement in cardiac function. No patients experienced major organ deterioration during the reported follow‑up period.
What is known about safety in this setting?
Across both dose levels in LINKER‑AL2, all patients experienced at least one treatment‑emergent adverse event, which is expected in a heavily pretreated, high‑risk population. However, no dose‑limiting toxicities were seen in the preliminary dataset, and safety monitoring is ongoing as the Phase 2, registrational‑intent portion of the trial continues.
Roche
Roche highlights giredestrant’s evolving role in breast cancer treatment
Roche continues to build on its recent data, reinforcing giredestrant’s potential to reshape the treatment paradigm in early breast cancer and expand its role across advanced disease.
What is the mechanism of action of giredestrant?
Giredestrant is an investigational, oral, selective oestrogen receptor degrader (SERD) being developed for ER‑positive, HER2‑negative breast cancer across both early and advanced settings. This subtype accounts for about 70% of all breast cancers, and most patients are diagnosed at an early stage.
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Results from three Phase III trials will underpin future discussions on how giredestrant may become a key endocrine therapy option across multiple stages of disease:
lidERA Breast Cancer
Following the previously reported reduction in the risk of invasive disease recurrence or death, new lidERA data will continue to inform how giredestrant performs in both premenopausal and postmenopausal patients with early breast cancer. These findings will support ongoing regulatory and clinical discussions with the US FDA.
persevERA Breast Cancer
The persevERA primary results will remain important for understanding giredestrant in combination with palbociclib as a first‑line option for locally advanced or metastatic endocrine‑sensitive disease. Although the primary endpoint is not met, the numerical improvement in progression‑free survival suggests that giredestrant retains activity in the first‑line setting and may guide future study designs.
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evERA Breast Cancer
Updated post‑progression analyses from evERA will continue to highlight the sustained clinical benefit of giredestrant plus everolimus after prior CDK4/6 inhibitor therapy. These data support the recently accepted New Drug Application with the US FDA and will shape how the regimen is positioned in later‑line treatment strategies.