European Society for Medical Oncology (ESMO) Congress | ESMO 2025 | News | Updates | iPharmaCenter
- ipharmaservices
- Oct 18
- 20 min read
Updated: Oct 22
PFIZER
Xtandi Plus Leuprolide Cuts Risk of Death by 40% in Advanced Prostate Cancer, Delivering Unprecedented 8-Year Survival Benefit
Pfizer and Astellas have announced final overall survival (OS) results from the Phase 3 EMBARK trial, revealing that Xtandi (enzalutamide) in combination with leuprolide significantly prolonged survival in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC) who had high-risk biochemical recurrence (BCR).
Major Survival Advantage with Combination Therapy
The data showed that Xtandi plus leuprolide reduced the risk of death by 40.3% compared to leuprolide alone. After eight years of follow-up, 78.9% of patients receiving the combination therapy were alive, compared with 69.5% of those treated with leuprolide alone, marking a nearly 10% absolute improvement in survival.
This makes Xtandi the first and only androgen receptor inhibitor (ARI)-based regimen to show a statistically significant overall survival benefit in this patient population.
While Xtandi monotherapy also demonstrated a numerical improvement in OS versus leuprolide alone, the difference did not reach statistical significance. The median follow-up was approximately 94 months across all treatment arms.
Previous Results Showed Strong Metastasis-Free Survival
Earlier results from the EMBARK trial, published in The New England Journal of Medicine in 2023, demonstrated that Xtandi plus leuprolide achieved a 58% reduction in risk of metastasis or death compared with leuprolide alone. Xtandi monotherapy also outperformed leuprolide alone.
Those findings led to Xtandi’s 2023 approval for treating non-metastatic castration-sensitive prostate cancer with high-risk BCR, expanding its use beyond castration-resistant and metastatic hormone-sensitive disease settings.
A New Benchmark for Early Intervention: The long-term survival benefit observed with Xtandi plus leuprolide underscores the potential of earlier use of androgen receptor inhibitors in prostate cancer management. By delaying metastasis and extending life expectancy, this combination could reshape treatment standards for men with high-risk, non-metastatic hormone-sensitive prostate cancer.
Pfizer’s Braftovi and Mektovi Combination Shows Impressive Four-Year Survival in Advanced Lung Cancer Patients
Pfizer has reported new long-term results from its Phase 2 PHAROS study, highlighting that the combination of Braftovi (encorafenib) and Mektovi (binimetinib) delivers sustained survival benefits for people living with metastatic non-small cell lung cancer (mNSCLC) harboring the BRAF V600E mutation.
Strong Long-Term Outcomes
After roughly four years of follow-up, patients who had not received prior treatment achieved a median overall survival (OS) of 47.6 months, with 49% still alive at the four-year mark. Among those previously treated, the median OS reached 22.7 months, and 31% remained alive at four years. These results underline the lasting efficacy of the dual-targeted approach.
Study Overview
The PHAROS trial (NCT03915951) is an open-label, multicenter, single-arm study designed to evaluate the safety and effectiveness of Braftovi plus Mektovi in both newly diagnosed and previously treated patients with BRAF V600E-mutant metastatic NSCLC.
Based on earlier findings from this same study, the U.S. FDA approved the combination in October 2023, followed by European Commission approval in August 2024. These decisions were supported by the trial’s objective response rate (ORR) and duration of response (DoR) data, which served as key efficacy measures.
Efficacy Results
In the PHAROS study:
The ORR was 75% (95% CI: 62–85) among treatment-naïve patients (n=59).
The ORR was 46% (95% CI: 30–63) among previously treated patients (n=39).
Setting a New Benchmark for Targeted Therapies
The new PHAROS findings strengthen evidence that Braftovi plus Mektovi provides a durable and clinically meaningful benefit, potentially setting a new standard for targeted treatment in patients with BRAF V600E-mutated metastatic NSCLC.
Precision Medicine in Lung Cancer
Advances in molecular profiling have transformed NSCLC management, enabling more personalized treatment strategies. Though BRAF V600E mutations occur in only about 2% of NSCLC cases, they make up roughly half of all BRAF-mutated forms of metastatic disease—highlighting the critical need for effective targeted therapies like Braftovi and Mektovi.
Padcev and Keytruda Combination Before and After Surgery Reduces Bladder Cancer Recurrence and Death Risk by Up to 60%
A Phase 3 clinical study (EV-303 / KEYNOTE-905) has shown that the combination of Padcev (enfortumab vedotin) and Keytruda (pembrolizumab) significantly improves outcomes for patients with muscle-invasive bladder cancer (MIBC) who are not candidates for cisplatin-based chemotherapy.
Major Improvements in Survival Outcomes
According to the first interim analysis, patients treated with Padcev plus Keytruda experienced a 60% lower risk of cancer recurrence, progression, or death compared with those who underwent surgery alone.
At two years, 74.7% of patients receiving the combination remained event-free, compared with only 39.4% in the surgery-only group. The median event-free survival (EFS) for the combination group has not yet been reached, while it was 15.7 months for surgery alone.
The combination therapy also achieved a 50% reduction in the risk of death compared to surgery alone. After two years, nearly 80% of patients treated with PADCEV plus Keytruda were alive, versus 63.1% of those who received only surgical treatment.
Benefits Across Multiple Patient Subgroups
Consistent improvements in both EFS and overall survival (OS) were seen across all predefined categories, including age, gender, smoking history, PD-L1 status, and cisplatin eligibility. Benefits were also consistent regardless of disease stage and geographic region.
Regulatory Pathway and Next Steps
While PADCEV plus Keytruda is not yet approved as a perioperative (pre- and post-surgical) therapy for cisplatin-ineligible MIBC patients, these compelling data will be shared with global regulatory authorities as part of upcoming submissions.
In parallel, the same drug combination is being tested in cisplatin-eligible patients in the EV-304 (KEYNOTE-B15) Phase 3 trial to explore its potential across a broader range of bladder cancer patients.
A Potential New Standard of Care
The EV-303 trial results demonstrate unprecedented survival outcomes, suggesting that PADCEV plus Keytruda could soon reshape the treatment landscape for patients with muscle-invasive bladder cancer who have limited therapeutic options.
ASTRAZENECA
Datroway Extends Survival by Five Months Over Chemotherapy in 1st-Line Treatment of Metastatic TNBC
AstraZeneca and Daiichi Sankyo announced that their antibody-drug conjugate Datroway (datopotamab deruxtecan) delivered a major survival advantage in the Phase III TROPION-Breast02 trial, marking a significant milestone for patients with metastatic triple-negative breast cancer (TNBC) who have limited treatment options and are ineligible for immunotherapy.
Results showed that Datroway extended median overall survival (OS) by five months compared with standard chemotherapy - 23.7 months versus 18.7 months, representing a 21% reduction in the risk of death.
The therapy also achieved a 43% reduction in the risk of disease progression or death, with median progression-free survival (PFS) of 10.8 months compared with 5.6 months for chemotherapy, as confirmed by blinded independent central review.
In addition, Datroway delivered a confirmed objective response rate (ORR) of 62.5%, more than double the 29.3% seen with chemotherapy.
The study included patients with locally recurrent, inoperable, or metastatic TNBC who could not receive immunotherapy, including those with PD-L1–positive tumors who were unsuitable for such treatment.
Datroway is now the first and only therapy to demonstrate a statistically significant and clinically meaningful overall survival benefit over chemotherapy in this challenging TNBC population, underscoring its potential to redefine the first-line treatment landscape for these patients.
Enhertu Delivers Major Reduction in Disease Recurrence Risk for High-Risk HER2-Positive Early Breast Cancer
New data from the Phase III DESTINY-Breast05 clinical trial revealed that Enhertu (trastuzumab deruxtecan) significantly decreased the likelihood of disease recurrence or death by 53% compared with trastuzumab emtansine (T-DM1) in patients with high-risk HER2-positive early breast cancer following neoadjuvant therapy.
Presented during the ESMO Presidential Symposium alongside findings from DESTINY-Breast11, the results further support Enhertu’s potential to become a key therapy in the curative-intent treatment landscape for early-stage breast cancer.
The DESTINY-Breast05 study evaluated Enhertu as an adjuvant option (post-surgery) in patients whose cancer persisted in the breast and/or lymph nodes after neoadjuvant therapy. Results demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS). Patients receiving Enhertu were 53% less likely to experience invasive disease recurrence or death than those treated with T-DM1.
After three years, 92.4% of patients on Enhertu remained alive without invasive disease compared to 83.7% of those receiving T-DM1. The IDFS advantage was consistently observed across all predefined patient subgroups.
Enhertu also demonstrated strong benefits in additional endpoints. Disease-free survival (DFS) improved by 53% (HR 0.47; 95% CI 0.34–0.66; p<0.0001), while the risk of distant recurrence was reduced by 51%, and the likelihood of developing brain metastases dropped by 36% versus T-DM1.
At the time of the interim analysis, overall survival (OS) data were not yet mature (2.9% maturity at data cutoff) and will be further evaluated as follow-up continues.
Key Outcomes at 3 Years:
Invasive Disease-Free Survival (IDFS): 92.4% (Enhertu) vs. 83.7% (T-DM1)
Disease-Free Survival (DFS): 92.3% (Enhertu) vs. 83.5% (T-DM1)
Overall Survival (OS): 97.4% (Enhertu) vs. 95.7% (T-DM1)
These results mark a major advancement for Enhertu, highlighting its potential to redefine the standard of care for patients with high-risk HER2-positive early breast cancer.
Enhertu-Based Regimen Achieves Record Pathologic Complete Response in High-Risk HER2-Positive Early Breast Cancer
New findings from the Phase III DESTINY-Breast11 trial reveal that Enhertu (trastuzumab deruxtecan) administered prior to surgery and followed by a combination of paclitaxel, trastuzumab, and pertuzumab (THP) achieved a pathologic complete response (pCR) in 67% of patients with high-risk HER2-positive early-stage breast cancer. These results represent the highest pCR rate ever recorded in a Phase III registrational trial for this patient population, highlighting a potentially transformative approach to treatment.
Significant Efficacy Over Standard Chemotherapy
DESTINY-Breast11 compared Enhertu followed by THP against the standard neoadjuvant regimen of dose-dense doxorubicin plus cyclophosphamide followed by THP (ddAC-THP). Patients receiving the Enhertu-based sequence achieved a pCR rate of 67.3%, compared with 56.3% in the ddAC-THP arm—an absolute improvement of 11.2%.
The improvement was consistent across subgroups:
Hormone receptor (HR)-positive: 61.4% (Enhertu) vs. 52.3% (ddAC-THP)
HR-negative: 83.1% (Enhertu) vs. 67.1% (ddAC-THP)
Minimal Residual Disease After Surgery
After surgery, 81.3% of patients who received the Enhertu-based regimen showed no or minimal remaining invasive cancer (residual cancer burden [RCB] 0+I), compared with 69.1% in the ddAC-THP arm, a 12.2% improvement.
Across subgroups:
HR-positive patients: 78.0% vs. 64.7%
HR-negative patients: 90.4% vs. 81.2%
Early Event-Free Survival Data
While event-free survival (EFS) results remain immature (4.5% maturity at cutoff), early trends favored Enhertu followed by THP over ddAC-THP, with two-year EFS rates of 96.9% vs. 93.1%, respectively.
JOHNSON AND JOHNSON
Subcutaneous Amivantamab Shows Encouraging 45% Response Rate in Advanced Head and Neck Cancer
Johnson & Johnson announced new data from the Phase 1b/2 OrigAMI-4 study, revealing that a subcutaneous (SC) formulation of amivantamab achieved a 45% overall response rate (ORR) and a median response duration of 7.2 months in patients with human papillomavirus (HPV)-unrelated recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) who had already progressed on both checkpoint inhibitor and platinum-based chemotherapy.
Strong Efficacy and Convenient Administration
The new SC formulation of amivantamab can be administered as a manual injection in just five minutes, providing a simpler alternative to the intravenous (IV) form of RYBREVANT (amivantamab-vmjw), which is already approved for non-small cell lung cancer (NSCLC).
In Cohort 1 of the OrigAMI-4 trial, 38 patients with HPV-unrelated R/M HNSCC received SC amivantamab every three weeks (2400 mg, or 3360 mg for patients ≥80 kg). Results demonstrated:
Overall response rate (ORR): 45%
Median time to first response: 6.4 weeks
Median duration of response (DOR): 7.2 months
Tumor shrinkage: observed in 82% of patients
Median progression-free survival (PFS): 6.8 months
Median overall survival (OS): not yet reached
Addressing an Area of High Unmet Need
Patients with recurrent or metastatic HNSCC who no longer respond to checkpoint inhibitors or platinum-based regimens face limited therapeutic options, with typical response rates between 10% and 24% and median survival of 6–9 months. Outcomes are even poorer for those with HPV-unrelated disease. These patients often experience severe symptoms including pain, fatigue, and difficulty swallowing or speaking.
Head and neck tumors commonly overexpress EGFR and MET, both of which play key roles in tumor progression. Amivantamab, a bispecific antibody targeting EGFR and MET, is designed to block these signaling pathways while engaging the immune system to attack cancer cells.
Expanding Development to Phase 3
Following the positive Phase 1b/2 results, Johnson & Johnson has initiated the OrigAMI-5 Phase 3 study, which will evaluate first-line SC amivantamab in combination with pembrolizumab and carboplatin compared with 5-fluorouracil (5-FU) plus pembrolizumab and platinum-based chemotherapy (cisplatin or carboplatin) in patients with HPV-unrelated R/M HNSCC.
About the OrigAMI-4 Study: The OrigAMI-4 trial (NCT06385080) is a multicenter, open-label Phase 1b/2 study exploring subcutaneous amivantamab in multiple patient cohorts with recurrent or metastatic HNSCC. Cohort 1 specifically included individuals with HPV-unrelated disease who had received both platinum-based chemotherapy and PD-1/PD-L1 immunotherapy, but not prior anti-EGFR therapy. Treatment was given every three weeks (Q3W), and the primary endpoint was overall response rate (ORR), as assessed by blinded independent central review (BICR) using RECIST v1.1 criteria.
These findings underscore the potential of subcutaneous amivantamab as a more convenient and effective option for patients with advanced head and neck cancer, expanding the reach of a therapy already proven in lung cancer to a broader range of solid tumors.
Johnson & Johnson’s Inlexzo and Cetrelimab Combination Shows Strong Tumor Response Before Surgery in Muscle-Invasive Bladder Cancer
Johnson & Johnson announced encouraging results from the Phase 2b SunRISe-4 trial, where the combination of INLEXZO (gemcitabine intravesical system) and cetrelimab (CET) achieved promising tumor clearance in patients with muscle-invasive bladder cancer (MIBC) who were scheduled for radical cystectomy but could not receive, or declined, platinum-based chemotherapy.
Promising Pre-Surgical Outcomes
According to the primary analysis, 38% of patients treated with INLEXZO plus cetrelimab had no detectable cancer remaining in the bladder before surgery, achieving what’s known as a pathologic complete response (pCR). Those treated with cetrelimab alone demonstrated a 28% pCR rate.
Additionally, the pathologic overall response (pOR)—defined as tumor downstaging to non–muscle-invasive disease (≤pT1)—was 53% in the combination group and 44% in the cetrelimab-only group. After one year, recurrence-free survival (RFS) rates were 77% for patients receiving the combination and 64% for those treated with cetrelimab alone.
About the SunRISe-4 Study
The SunRISe-4 (NCT04919512) study is an open-label, randomized, multicenter Phase 2b trial evaluating the efficacy and safety of neoadjuvant INLEXZO plus cetrelimab or cetrelimab alone in patients with non-metastatic MIBC undergoing surgery.
In this analysis:
Cohort 1 (n=101) received four cycles of INLEXZO (225 mg of gemcitabine) delivered via a bladder catheter, combined with 360 mg IV cetrelimab every 21 days.
Cohort 2 (n=58) received cetrelimab monotherapy (360 mg IV) every 21 days for the same duration.
SunRISe-4 is not a registration trial for either INLEXZO or cetrelimab but provides valuable insights into the role of neoadjuvant immunotherapy and localized drug delivery in this difficult-to-treat population.
About INLEXZO
INLEXZO is an FDA-approved intravesical therapy for adults with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. The device-based system continuously releases gemcitabine directly into the bladder, allowing sustained drug exposure and targeted anti-tumor activity.
These findings from SunRISe-4 demonstrate the potential of combining localized drug delivery (INLEXZO) with systemic immunotherapy (cetrelimab) to achieve meaningful tumor reduction prior to surgery. If further validated in larger trials, this approach could open new avenues for cisplatin-ineligible MIBC patients, who currently have limited neoadjuvant treatment options.
NOVARTIS
Novartis’ Kisqali Demonstrates Durable Five-Year Benefit in Early Breast Cancer, Reducing Risk of Recurrence by 28%
Novartis has announced new five-year findings from the Phase III NATALEE trial, showing that Kisqali (ribociclib) in combination with endocrine therapy (ET) delivers a sustained and clinically meaningful reduction in disease recurrence among patients with hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (EBC) - the most common breast cancer subtype.
Durable Long-Term Protection Against Recurrence
At a median follow-up of 58.4 months, data showed that Kisqali plus ET reduced the risk of recurrence by 28.4% compared with ET alone. The five-year invasive disease-free survival (iDFS) rates were 85.5% for patients receiving the Kisqali regimen versus 81.0% for those on ET alone — a 4.5% absolute improvement.
This benefit was consistent across key subgroups:
Stage II disease: 3.7% absolute improvement
Stage III disease: 5.6% absolute improvement
Node-negative patients: 5.7% absolute improvement
Node-positive patients (N1–N3): 4.4% absolute improvement
Kisqali also demonstrated a 29.1% reduction in distant disease-free survival (DDFS) events, further emphasizing its potential to prevent metastatic recurrence. Early data also suggested a favorable trend in overall survival (OS).
Broadest Patient Population Evaluated
The NATALEE study is the largest and most inclusive adjuvant trial conducted to date for a CDK4/6 inhibitor, enrolling patients with stage II and III HR+/HER2- early breast cancer, including those with node-negative disease-a group not previously studied in similar trials.
Continued Safety and Tolerability
The updated analysis, conducted roughly two years after all patients completed their three-year Kisqali treatment, confirmed no new long-term safety concerns. Kisqali maintained a well-characterized and manageable safety profile.
Setting a New Standard for Early Breast Cancer
Kisqali remains the only CDK4/6 inhibitor to show consistent, statistically significant survival benefits across three major Phase III trials,MONALEESA-2, MONALEESA-3, and MONALEESA-7—in advanced HR+/HER2- breast cancer.
How Kisqali Works
Kisqali is a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that helps slow tumor growth by blocking proteins that drive cell cycle progression in cancer cells.
The five-year NATALEE data reinforce Kisqali’s potential to become a foundational therapy in the early breast cancer setting, helping patients stay disease-free longer and reducing the risk of recurrence across the broadest range of HR+/HER2- early-stage disease.
Novartis’ Pluvicto Shows Significant Delay in Disease Progression in Metastatic Prostate Cancer
Novartis has unveiled new findings from the Phase III PSMAddition trial, showing that Pluvicto (lutetium-177 vipivotide tetraxetan), when combined with standard of care (SoC) - consisting of an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) - substantially slows disease progression in patients with prostate-specific membrane antigen (PSMA)-positive metastatic hormone-sensitive prostate cancer (mHSPC).
Pluvicto Significantly Improves Progression-Free Survival
Results demonstrated that the Pluvicto-based combination reduced the risk of radiographic progression or death by 28% compared to SoC alone, marking a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS).
An early positive trend in overall survival (OS) was also observed, with a hazard ratio of 0.84, although data remain immature. Additionally, patients receiving Pluvicto plus SoC achieved higher complete response rates (57.1% vs. 42.3%) and greater overall response rates (85.3% vs. 80.8%) than those treated with SoC alone.
Pluvicto also delayed the transition to metastatic castration-resistant prostate cancer (mCRPC), reducing risk by 30% (HR 0.70; 95% CI: 0.58–0.84). The benefits were consistent across all pre-defined patient subgroups.
Addressing an Unmet Need in Early Metastatic Disease
Every year, an estimated 172,000 men in the U.S., Europe, and Asia are diagnosed with mHSPC. Most eventually progress to mCRPC, often within 20 months, where prognosis worsens significantly, with life expectancy dropping below two years. This transition is associated with greater symptom burden, declining quality of life, and limited treatment options.
Because over 80% of prostate cancers highly express the PSMA biomarker, PSMA-targeted therapies like Pluvicto represent a promising approach to treating the disease earlier in its course.
About the PSMAddition Trial
The PSMAddition study (NCT04720157) is a global, open-label, randomized Phase III trial evaluating Pluvicto plus SoC (ARPI + ADT) versus SoC alone in patients with PSMA-positive mHSPC. The primary endpoint is radiographic progression-free survival (rPFS), measured by PCWG3-modified RECIST v1.1 criteria as assessed by blinded independent central review (BICR). Overall survival (OS) serves as a key secondary endpoint.
The study is ongoing and has enrolled 1,144 participants across 20 countries.
How Pluvicto Works
Pluvicto is a radioligand therapy (RLT) designed to deliver targeted radiation to PSMA-expressing cancer cells. It combines a PSMA-targeting ligand with the radioactive isotope lutetium-177. Once infused, the drug binds to PSMA on tumor cells, releasing beta radiation that damages cancer cells and surrounding tumor tissue, ultimately inhibiting replication and inducing cell death.
LILLY
Lilly’s Verzenio Shows Long-Term Survival Advantage in Early Breast Cancer
Eli Lilly announced new findings from the Phase 3 monarchE trial showing that Verzenio (abemaciclib) combined with endocrine therapy significantly improved overall survival in patients with hormone receptor-positive (HR+), HER2-negative, high-risk early breast cancer. Lilly stated that Verzenio is now the first modern treatment in more than 20 years to demonstrate a meaningful overall survival benefit in this patient population.
The updated analysis, presented after a median follow-up of 6.3 years, revealed that two years of adjuvant treatment with Verzenio plus endocrine therapy reduced the risk of death by 15.8% compared with endocrine therapy alone. The seven-year overall survival rate was 86.8% for patients receiving Verzenio versus 85.0% for those on endocrine therapy alone.
Beyond overall survival, the combination therapy continued to demonstrate strong, lasting improvements in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS). The data showed a sustained reduction in recurrence risk, with 32% fewer patients in the Verzenio group living with metastatic disease compared to those treated with endocrine therapy alone (6.4% vs. 9.4%).
More than three-quarters of patients were followed for at least four years after completing Verzenio treatment, further supporting the long-term benefit of the therapy. Consistent results were observed across the intent-to-treat population and key subgroups, including Cohort 1.
These findings reinforce Verzenio’s role as an important advancement in the treatment of HR+, HER2-negative, high-risk early breast cancer, offering patients not only longer disease-free survival but also a significant improvement in overall survival.
MERCK
Raludotatug Deruxtecan Shows Promising Efficacy in Platinum-Resistant Ovarian, Primary Peritoneal, and Fallopian Tube Cancers in Phase 2 REJOICE-Ovarian01 Study
Results from the Phase 2 portion of the REJOICE-Ovarian01 Phase 2/3 trial demonstrated that raludotatug deruxtecan (R-DXd) achieved significant clinical responses in patients with recurrent platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers.
Raludotatug deruxtecan is an innovative CDH6-targeting DXd antibody-drug conjugate (ADC), designed by Daiichi Sankyo and co-developed with Merck (known as MSD outside the U.S. and Canada). The therapy is being investigated as a potential first-in-class treatment option for patients whose disease has progressed after standard platinum-based regimens.
Significant Unmet Need in Advanced Ovarian Cancer
Patients with advanced ovarian cancer often face poor prognoses after recurrence. Median overall survival can be as short as two years, with only around 31.8% surviving five years after diagnosis with distant-stage disease. Moreover, 70–80% of patients eventually experience disease progression following first-line platinum chemotherapy, emphasizing the urgent need for novel therapies.
Encouraging Phase 2 Results:
Across all tested dose levels (4.8 mg/kg, 5.6 mg/kg, and 6.4 mg/kg), R-DXd achieved a confirmed objective response rate (ORR) of 50.5% in 107 patients, according to blinded independent central review (BICR). The trial recorded 3 complete responses (CRs) and 51 partial responses (PRs), resulting in a disease control rate (DCR) of 77.6%.
At the 5.6 mg/kg dose—selected for further evaluation in Phase 3, 50.0% of patients achieved a confirmed response, including 2 complete and 16 partial responses, with a DCR of 80.6%. Notably, responses were observed across different CDH6 expression levels and were consistent across doses, indicating robust antitumor activity.
KEYTRUDA Combination Demonstrates Significant Survival Benefit in Platinum-Resistant Recurrent Ovarian Cancer in Phase 3 KEYNOTE-B96 Trial
Merck announced new findings from the pivotal Phase 3 KEYNOTE-B96 (ENGOT-ov65) study evaluating Keytruda (pembrolizumab), the company’s anti–PD-1 therapy, in combination with chemotherapy (paclitaxel) with or without bevacizumab, in patients with platinum-resistant recurrent ovarian cancer. The data mrks the first time an immune checkpoint inhibitor-based regimen has demonstrated statistically significant improvements in progression-free survival (PFS) for all enrolled patients and in overall survival (OS) for those with PD-L1–expressing tumors, compared with placebo plus chemotherapy with or without bevacizumab.
Based on these results, the U.S. Food and Drug Administration (FDA) has accepted a priority review of a supplemental Biologics License Application (sBLA) for KEYTRUDA in combination with chemotherapy, with or without bevacizumab, for eligible patients with platinum-resistant recurrent ovarian cancer.
Also read: FDA Approves Johnson & Johnson’s Simponi (golimumab) as the First Monthly Maintenance Therapy for Pediatric Ulcerative Colitis
At the first interim analysis (median follow-up: 15.6 months), the combination of Keytruda and chemotherapy with or without bevacizumab (n=322) showed a 30% reduction in the risk of disease progression or death compared to the placebo regimen. The 12-month PFS rate was 33.1% for patients treated with the Keytruda regimen versus 21.3% for those on placebo.
Among patients whose tumors expressed PD-L1 (CPS ≥1), the KEYTRUDA combination (n=234) reduced the risk of disease progression or death by 28% compared with the control group (n=232). The 12-month PFS rates in this subgroup were 35.2% versus 22.6%, respectively.
At the second interim analysis (median follow-up: 26.6 months), the Keytruda regimen demonstrated a 24% reduction in the risk of death among PD-L1–positive patients. The 12-month OS rate for the Keytruda arm was 69.1% compared with 59.3% for placebo, and the 18-month OS rates were 51.5% and 38.9%, respectively.
These findings establish KEYNOTE-B96 as the first Phase 3 trial to confirm meaningful survival benefits for an immunotherapy-based approach in this challenging ovarian cancer population.
ROCHE
Roche Reports Positive Phase III Results for Giredestrant Combination in Advanced ER-Positive Breast Cancer
Roche has announced encouraging findings from its Phase III evERA Breast Cancer trial, demonstrating that the investigational therapy giredestrant—an oral selective estrogen receptor degrader (SERD)-when combined with everolimus, produced a significant improvement in progression-free survival (PFS) in individuals with estrogen receptor (ER)-positive, HER2-negative advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor and endocrine therapy.
According to the study, the giredestrant–everolimus combination lowered the likelihood of disease progression or death by 44% in the overall population and by 62% in participants with ESR1 mutations, compared with standard endocrine therapy plus everolimus. These results make evERA the first head-to-head Phase III trial to demonstrate clear superiority of a SERD-containing regimen over current standard-of-care combinations in this setting.
Also read: Daiichi Sankyo Advances Breast Cancer Portfolio Expansion with ENHERTU approaval in Japan and DATROWAY's positive study
Efficacy Outcomes
Participants receiving giredestrant with everolimus achieved a median PFS of 8.77 months, versus 5.49 months in those on standard treatment. Among the ESR1-mutated subgroup, median PFS was 9.99 months for the giredestrant arm and 5.45 months for the control arm. The PFS advantage was consistent across all analyzed patient subgroups.
Early overall survival (OS) data showed an emerging positive signal in both study populations:
Intention-to-treat (ITT): HR = 0.69
ESR1-mutated: HR = 0.62
Clinical Significance
ER-positive breast cancer represents roughly 70% of all breast cancer cases. In patients previously treated with CDK4/6 inhibitors, resistance to endocrine therapies often limits treatment options and contributes to disease progression. The all-oral regimen of giredestrant plus everolimus offers a convenient, injection-free approach that targets complementary signaling pathways, potentially improving both efficacy and patient quality of life.
If approved, this would be the first and only oral SERD-based combination therapy available for patients with ER-positive advanced breast cancer after CDK4/6 inhibitor therapy.
About the evERA Breast Cancer Study
The evERA Breast Cancer study (NCT05306340) is a global, open-label, randomized Phase III trial assessing the safety and efficacy of giredestrant plus everolimus versus standard endocrine therapy plus everolimus in individuals with ER-positive, HER2-negative locally advanced or metastatic breast cancer who have received prior endocrine and CDK4/6 inhibitor therapy.
The co-primary endpoints are investigator-assessed progression-free survival in the ITT and ESR1-mutated populations. Secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate, and safety. The trial intentionally included a higher proportion of ESR1-mutated participants-who make up approximately 40% of post-CDK inhibitor ER-positive cases-to better evaluate the treatment’s effect in this subgroup.
About Giredestrant
Giredestrant is an investigational oral next-generation selective estrogen receptor degrader and antagonist designed to block estrogen binding, degrade the receptor, and suppress tumor cell growth. Roche’s comprehensive clinical development program for giredestrant spans multiple breast cancer settings and therapy lines, reinforcing its commitment to advancing novel endocrine treatment options for patients with ER-positive disease.
Tecentriq Significantly Improves Survival in Bladder Cancer Using ctDNA-Guided Treatment Strategy
Roche announced breakthrough findings from the Phase 3 IMvigor011 study, which evaluated Tecentriq (atezolizumab) as an adjuvant therapy for patients with muscle-invasive bladder cancer (MIBC) who had undergone surgery and tested positive for circulating tumor DNA (ctDNA), an indicator of minimal residual disease.
Strong Survival Outcomes
The study revealed that patients treated with Tecentriq experienced a 41% lower risk of death and a 36% lower risk of disease recurrence or death compared with those given a placebo. These results mark a major step forward for post-surgery management in bladder cancer using a ctDNA-guided treatment approach.
At a median follow-up of 16.1 months, the median disease-free survival (DFS) was 9.9 months for Tecentriq-treated patients versus 4.8 months for those on placebo. The median overall survival (OS) reached 32.8 months with Tecentriq, compared to 21.1 months in the placebo arm.
Importantly, patients who consistently showed no detectable ctDNA after surgery had a much lower likelihood of disease recurrence, underscoring the value of this biomarker-driven strategy.
A First-of-Its-Kind Precision Approach
The IMvigor011 trial is the first global Phase 3 study to successfully demonstrate a benefit for ctDNA-guided adjuvant immunotherapy in bladder cancer. This approach used Natera’s Signatera™ Molecular Residual Disease (MRD) test, allowing physicians to identify patients at high risk of relapse and spare those at low risk from unnecessary treatment and potential side effects.
Study Design
IMvigor011 (NCT04660344) was a randomized, double-blind, placebo-controlled global trial enrolling patients with ctDNA-positive MIBC who had previously undergone radical cystectomy. The study included 761 patients in its monitoring phase, with 250 ctDNA-positive participants moving on to the treatment phase, where they received either Tecentriq or placebo.
The primary endpoint was disease-free survival, while secondary endpoints included overall survival, safety, and other clinical measures.
Transforming Bladder Cancer Care
Each year, more than 150,000 people worldwide are diagnosed with MIBC, a highly aggressive cancer with limited treatment options and poor long-term survival. The IMvigor011 results highlight the potential of ctDNA-guided therapy to transform the treatment paradigm, allowing clinicians to personalize care, improve survival outcomes, and reduce overtreatment.
If approved, this innovative approach combining Tecentriq with ctDNA testing could mark a new era of precision medicine in bladder cancer management.
BMS
SystImmune and Bristol Myers Squibb Present First Global Phase I Data for Iza-bren, an EGFR x HER3 Bispecific Antibody-Drug Conjugate, in Advanced Solid Tumors at ESMO 2025
SystImmune Inc., and Bristol Myers Squibb have shared the first global Phase I results for iza-bren (BL-B01D1), a dual-target EGFR x HER3 antibody-drug conjugate (ADC).
The data, presented from the US-Lung-101 Phase I trial (NCT05983432), mark the first global presentation of iza-bren’s clinical performance, highlighting both safety and early efficacy outcomes in patients with advanced or metastatic solid tumors. The treatment is being co-developed by SystImmune and Bristol Myers Squibb through an exclusive collaboration outside Mainland China. In August 2025, the U.S. Food and Drug Administration (FDA) awarded iza-bren Breakthrough Therapy Designation for patients with previously treated EGFR-mutated non-small cell lung cancer (NSCLC), based on results from Chinese and global studies.
The ongoing study investigates iza-bren in patients with heavily pretreated metastatic or unresectable solid tumors, including NSCLC. As of the July 23, 2025 data cut-off, the therapy demonstrated:
Encouraging anti-tumor activity in patients who had received multiple prior treatments, across both EGFR-mutated and wild-type NSCLC.
A manageable safety profile, primarily involving hematologic side effects that responded well to standard interventions. Notably, no cases of interstitial lung disease were reported.
Among the 107 enrolled participants, most had advanced disease and extensive prior therapy exposure. The most frequent treatment-related adverse events were blood-related, including neutropenia, which were largely manageable and rarely required dose modification. Preventive strategies for neutropenia have now been integrated into ongoing trials to further improve safety.
In patients treated with the 2.5 mg/kg dosing regimen (Days 1 and 8 every three weeks), 55% (11 out of 20) achieved confirmed responses, with a median progression-free survival of 5.4 months. Confirmed responses were observed in both EGFR-mutated (3 of 10) and EGFR wild-type (3 of 4) NSCLC groups.
Building on these results, multiple global registrational studies are underway:
IZABRIGHT-Breast01 (NCT06926868) – first-line metastatic triple-negative breast cancer
IZABRIGHT-Lung01 (NCT05983432) – second-line metastatic EGFR-mutant NSCLC
IZABRIGHT-Bladder01 (NCT07106762) – second-line metastatic urothelial carcinoma
The BL-B01D1-LUNG-101 study is a global, multicenter, Phase I trial designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of iza-bren in patients with metastatic or inoperable NSCLC and other solid tumors. The trial explores two dosing regimens—administering the drug either on Days 1 and 8 or only on Day 1 of a 21-day cycle—and includes dose escalation, dose finding, and dose expansion phases.
Key study goals include assessing safety as the primary endpoint, while secondary measures encompass objective response rate (ORR) per RECIST 1.1 criteria, duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetic (PK) profiles.
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