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American Society of Clinical Oncology (ASCO) | 2024 | News | Updates |iPharmaCenter

Updated: Jun 6

Bristol Myers Squibb Announces Superior Survival Outcomes with Opdivo Plus Yervoy Over Lenvatinib or Sorafenib for Advanced Hepatocellular Carcinoma in CheckMate -9DW Trial


Bristol Myers Squibb has unveiled groundbreaking results from the Phase 3 CheckMate -9DW trial, demonstrating that the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) significantly enhances overall survival in patients with advanced hepatocellular carcinoma (HCC) compared to lenvatinib or sorafenib.


The dual immunotherapy approach with Opdivo and Yervoy not only improved overall survival but also achieved a higher objective response rate (ORR) and longer response duration than the treatments of lenvatinib or sorafenib in this patient group.

Study Highlights:

  • Improved Overall Survival (OS):

  • The median OS for patients treated with Opdivo plus Yervoy was 23.7 months (95% CI: 18.8–29.4), compared to 20.6 months (95% CI: 17.5–22.5) for those receiving lenvatinib or sorafenib.

  • The hazard ratio (HR) for overall survival was 0.79 (95% CI: 0.65–0.96; p = 0.018), indicating a statistically significant and clinically meaningful benefit.

  • The survival advantage was consistent across various patient subgroups.

  • Enhanced Objective Response Rate (ORR):

  • The ORR for Opdivo plus Yervoy was 36% (95% CI: 31-42), markedly higher than the 13% (95% CI: 10-17) observed with lenvatinib or sorafenib.

  • Complete Response (CR) Rates and Response Durability:

  • Complete response rates were higher with Opdivo plus Yervoy at 7% compared to 2% with lenvatinib or sorafenib.

  • Among those who responded, the median duration of response was 30.4 months (95% CI: 21.2-NE) for Opdivo plus Yervoy, versus 12.9 months (95% CI: 10.2-31.2) for lenvatinib or sorafenib.

  • Symptom Deterioration: Treatment-related adverse events (TRAEs) of any grade were reported in 84% of patients on Opdivo plus Yervoy and 91% on lenvatinib or sorafenib. Grade 3/4 TRAEs occurred in 41% of patients treated with Opdivo plus Yervoy and 42% with lenvatinib or sorafenib.

  • Patients receiving Opdivo plus Yervoy had a 24% reduced risk of symptom deterioration (HR: 0.76, 95% CI: 0.62-0.93; p = 0.0059).


 

Promising New Data on Kite’s Yescarta for Relapsed/Refractory Central Nervous System Lymphoma

Kite has unveiled data from a pilot study conducted with Dana-Farber Cancer Institute. The study indicates that Yescarta (axicabtagene ciloleucel) is well-tolerated in patients with relapsed or refractory (R/R) primary or secondary central nervous system lymphoma (PCNSL and SCNSL).


Central nervous system lymphoma (CNSL) is a rare and aggressive type of non-Hodgkin lymphoma that either originates in (primary) or spreads to (secondary) the brain, eye, spinal cord, or cerebrospinal fluid. Historically, PCNSL has had a poor prognosis, with only 30% of patients surviving five years. More than half of the patients relapse after initial treatment, with a median survival of about two months. There is currently no standard treatment for R/R CNSL, making it a significant unmet clinical need.


The pilot study included 18 patients with CNSL. At a median follow-up of 24.2 months, there were no treatment-limiting toxicities or additional adverse event risks observed. Immune effector cell-associated neurologic syndrome (ICANS) occurred in 44% of patients, with 27.8% experiencing Grade 3 or higher ICANS.


The study reported an objective response rate of 94.4%, with 66.7% achieving complete response. The median time to best response was three months, and the median duration of response was 13.4 months. Nine patients experienced disease progression. At the median follow-up of 24 months, the median progression-free survival was 14.3 months (95% CI: 6.3-NR) and the median overall survival was 26.4 months (95% CI: 11.2-NR).


Ninety percent of patients developed Grade 1 or 2 cytokine release syndrome. Two patients had Ommaya-related meningitis, which required device removal but subsequently recovered.


 

Sustained Overall Survival Shown by Kite’s Tecartus in Adults with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

Kite, a subsidiary of Gilead (Nasdaq: GILD), has revealed updated four-year overall survival (OS) data from the pivotal ZUMA-3 study. This study evaluates the CAR T-cell therapy Tecartus (brexucabtagene autoleucel) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The updated findings show a median OS of 25.6 months and a four-year OS rate of 40% among all treated patients, with a safety profile consistent with the three-year analysis.


Study Details

In a poster presentation, data from patients treated with the pivotal dose of Tecartus in the pooled analysis of Phase 1 and 2 (n=78) were shared. The median follow-up period was 53.6 months (range 44.7-82.3) with a minimum follow-up of four years. Among all treated patients, the median OS was 25.6 months. For patients achieving complete remission or complete remission with incomplete hematologic recovery (n=57), the median OS was 47 months, the primary endpoint.


For patients younger than 26 years (n=15), the median OS (95% CI) was 23.2 months (9.0-NE). For those 26 years and older (n=63), the median OS was 26.0 months (15.9-NE). OS was a key secondary endpoint of the study.


Impact of Prior Therapies

Patients with one prior therapy (n=15) had a median OS (95% CI) of 60.4 months (7.6-NE), while those with two or more prior therapies (n=63) had a median OS of 25.4 months (15.9-47.0).


Blinatumomab Influence

For patients who had received prior blinatumomab (n=38), the median OS (95% CI) was 15.9 months (8.3-26.0). For those who had not (n=40), the median OS was 60.4 months (18.6-NE). The interpretation of these results is limited due to unbalanced patient characteristics and small sample sizes.


Transplant Outcomes

In patients who responded and subsequently underwent allogeneic stem cell transplant (n=14), the median OS (95% CI) was 36.3 months (10.2-NE). For responders who did not undergo transplant (n=43), the median OS was 60.4 months (23.2-NE).


No new adverse events or deaths have been reported since the three-year analysis.

 

Moderna and Merck Report Positive 3-Year Data for mRNA-4157 (V940) with KEYTRUDA in High-Risk Melanoma Patients

In a recent update, Moderna and Merck announced promising three-year data from their Phase 2b study involving mRNA-4157 (V940) in combination with KEYTRUDA (pembrolizumab) for high-risk Stage III/IV melanoma patients who have undergone complete resection. The combination therapy showed a significant reduction in the risks of recurrence, death, and distant metastasis compared to KEYTRUDA alone.


Study Findings

At a median follow-up of 34.9 months, the combination of mRNA-4157 (V940) and KEYTRUDA reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death by 62% compared to KEYTRUDA alone. The 2.5-year recurrence-free survival (RFS) rate was 74.8% for the combination therapy versus 55.6% for KEYTRUDA alone, with benefits observed across various exploratory subgroups.


Future Research

Following these encouraging results, Phase 3 studies for high-risk melanoma and non-small cell lung cancer are underway. Additionally, Phase 2 studies are being conducted for renal cell carcinoma and urothelial carcinoma, along with a Phase 2/3 study for cutaneous squamous cell carcinoma.


Detailed Results

This announcement marks the first presentation of findings from the planned analysis of the Phase 2b KEYNOTE-942/mRNA-4157-P201 study, which assessed mRNA-4157 (V940) combined with KEYTRUDA in patients with resected high-risk melanoma. With nearly three years of follow-up, the combination therapy continued to show significant and durable improvements in RFS, reducing recurrence or death by 49% and distant metastasis or death by 62% compared to KEYTRUDA alone.

These results build on previous data presented in 2023. The 2.5-year RFS rate was notably higher at 74.8% for the combination therapy compared to 55.6% for KEYTRUDA alone. The benefits were consistent across exploratory subgroups, irrespective of tumor mutational burden (TMB) or programmed death-ligand 1 (PD-L1) status.


Exploratory Analysis

The Phase 2b KEYNOTE-942/mRNA-4157-P201 study’s exploratory subgroup analysis revealed that the RFS benefit of the combination therapy was consistent across different TMB levels and PD-L1 statuses. However, the hazard ratio for circulating tumor DNA (ctDNA) positive patients was not estimable due to a small sample size. There were no significant links between individual human leukocyte antigen (HLA) alleles and RFS for the combination therapy.


Survival and Safety

The combination therapy also showed a favorable overall survival (OS) trend, with a 2.5-year OS rate of 96.0% compared to 90.2% for KEYTRUDA alone. The safety profile remained consistent with the primary analysis, with the most common adverse events being fatigue (60.6%), injection site pain (56.7%), and chills (49.0%).


 

Takeda and Pfizer Reveal Positive Four-Year Results from Phase 3 HD21 Trial of ADCETRIS (brentuximab vedotin) Combination in Frontline Hodgkin Lymphoma

Four-Year Study by GHSG Shows ADCETRIS + ECADD Combination Boosts Progression-Free Survival, Demonstrating Superior Efficacy and Manageable Safety Profile in Newly Diagnosed Stage IIb/III/IV Classical Hodgkin Lymphoma Patients Compared to eBEACOPP, a Standard Treatment in Europe


Takeda and Pfizer have announced that the German Hodgkin Study Group (GHSG) will present favorable results from the Phase 3 HD21 trial assessing ADCETRIS (brentuximab vedotin) in combination with chemotherapy.


The four-year analysis by GHSG revealed superior progression-free survival (PFS) and enhanced tolerability in patients compared to a current standard of care regimen in Europe for this condition.


The HD21 trial is a Phase 3, randomized, multi-nation, prospective, open-label study sponsored by GHSG and supported by Takeda. The study aims to compare ADCETRIS combined with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) against a standard treatment – escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (eBEACOPP) – in patients with newly diagnosed Stage IIb/III/IV classical Hodgkin lymphoma. At a preplanned three-year analysis, the study met its co-primary endpoints, with the ADCETRIS regimen showing significantly improved safety assessed by treatment-related morbidity (TRMB) and non-inferior PFS.


The findings indicated that including ADCETRIS in the chemotherapy regimen improved the risk-to-benefit profile of the combination treatment, maintaining effectiveness with significantly fewer acute and long-lasting treatment-related toxicities compared to the standard treatment.


The ASCO presentation details the four-year PFS analysis of the HD21 study conducted by GHSG. After 48 months, BrECADD exhibited superior efficacy over BEACOPP, with a 94.3% PFS for BrECADD compared to 90.9% for eBEACOPP. As previously noted in the three-year analysis, treatment with BrECADD was associated with a significant reduction in treatment-related morbidity (TRMB) compared to BEACOPP (n=738; 42% vs 59%; p<0.001), along with meaningful reductions in adverse events (AEs). The safety profile of ADCETRIS in patients receiving BrECADD remained consistent with other approved ADCETRIS combination regimens, with no new safety signals detected.


 

Novartis NATALEE Study: Kisqali Significantly Reduces Cancer Recurrence Risk in High-Risk, Node-Negative Breast Cancer Patients

A recent analysis from the NATALEE study by Novartis reveals that Kisqali (ribociclib), when added to endocrine therapy (ET), substantially lowers the risk of cancer recurrence in early-stage breast cancer patients with high-risk, node-negative disease.


The study highlighted that adding Kisqali to ET resulted in a 28% reduction in invasive disease-free survival (iDFS) risk for patients with node-negative (N0) disease who are at a high risk of recurrence. Currently, these patients are not eligible for CDK4/6 inhibitor treatments to manage recurrence risks, leaving a significant unmet need when treated with ET alone.


The efficacy, safety, and tolerability profile of Kisqali in this N0 disease subgroup aligns with the overall findings of the NATALEE study. This data suggests that the number of patients who could benefit from CDK4/6 inhibitors to reduce their recurrence risk could potentially double. Novartis has already submitted these findings to both the FDA and EMA.


In a detailed analysis of high-risk, node-negative (N0) hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) patients, Kisqali combined with ET showed significant improvements over ET alone in several key areas:

  • 3-year Invasive Disease-Free Survival (iDFS):

  • Kisqali + ET: 93.2%

  • ET alone: 90.6%

  • 3-year Distant Recurrence-Free Survival (DRFS):

  • Kisqali + ET: 96.3%

  • ET alone: 92.5%

  • 3-year Distant Disease-Free Survival (DDFS):

  • Kisqali + ET: 94.3%

  • ET alone: 91.5%


The safety profile of Kisqali at a 400 mg dose in the high-risk, N0 subgroup was consistent with previous findings, showing generally low-grade adverse events aside from laboratory results. Discontinuation rates due to all-grade adverse events were 24% for Kisqali plus ET compared to 8% for ET alone. No new safety concerns were identified.


 

Novartis Announces Phase III Data Showing Scemblix Outperforms Standard TKIs in Newly Diagnosed CML Patients

Novartis has revealed groundbreaking results from its Phase III ASC4FIRST trial, demonstrating that Scemblix (asciminib) significantly surpasses standard-of-care tyrosine kinase inhibitors (TKIs) in efficacy for adults with newly diagnosed chronic myeloid leukemia (CML).


The ASC4FIRST trial met both of its primary endpoints, showing clinically meaningful and statistically significant outcomes. Scemblix achieved superior major molecular response (MMR) rates at week 48 compared to investigator-selected standard TKIs, including imatinib, nilotinib, dasatinib, and bosutinib. Specifically, the MMR rate for Scemblix was 67.7% compared to 49.0% for the standard TKIs, and 69.3% compared to 40.2% for imatinib alone.


In addition to its superior efficacy, Scemblix demonstrated a favorable safety and tolerability profile. Patients treated with Scemblix experienced fewer grade ≥3 adverse events (AEs), required fewer dose adjustments, and had half the rate of treatment discontinuations compared to those on imatinib and second-generation TKIs (2G TKIs).


Despite advancements in CML treatment, there remains a significant unmet need as many newly diagnosed patients fail to achieve molecular response goals or discontinue treatment due to intolerance. The positive results from the ASC4FIRST trial highlight Scemblix's potential to address these challenges.


The median follow-up for the study was approximately 16 months for both Scemblix and the standard TKIs. Notably, nearly 20% more patients treated with Scemblix reached MMR at week 48 compared to those on standard TKIs, and nearly 30% more compared to those on imatinib alone. Scemblix also led to deeper molecular responses (MR4 and MR4.5) than both the standard TKIs and imatinib.


Primary Endpoints:

  • Week 48 MMR Rates:

  • Scemblix (n=201) vs. investigator-selected SoC TKIs: 67.7% vs. 49.0%

  • Scemblix (n=101) vs. imatinib (n=102): 69.3% vs. 40.2%

  • Week 48 MMR Treatment Difference:

  • Scemblix vs. investigator-selected SoC TKIs: 18.9%

  • Scemblix vs. imatinib: 29.6%

In newly diagnosed patients, the safety profile of Scemblix remained consistent with previous studies, with no new safety issues observed.


 

EVOKE-01 Study on Metastatic NSCLC Shows Promising Results at ASCO 2024

Gilead Sciences recently unveiled detailed findings from their Phase 3 EVOKE-01 study, which were presented at an oral session during the 2024 American Society of Clinical Oncology (ASCO) meeting. The study assessed the efficacy of Trodelvy (sacituzumab govitecan) in patients with metastatic non-small cell lung cancer (NSCLC) who had previously been treated.


The EVOKE-01 trial compared Trodelvy to docetaxel and found a 16% reduction in the risk of death among patients with advanced NSCLC that had progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy. The median overall survival (OS) was 11.1 months for those treated with Trodelvy, compared to 9.8 months for those on docetaxel. Although this improvement did not meet the primary endpoint of the study, it was consistent across both squamous and non-squamous histologies.


Particularly notable was the outcome for patients whose tumors did not respond to their last anti-PD-(L)1 treatment. This subgroup, which constituted about two-thirds of the study population, experienced a meaningful OS improvement of 3.5 months with Trodelvy (11.8 months) versus docetaxel (8.3 months). However, for patients whose tumors had responded to previous anti-PD-(L)1 therapy, the median OS was slightly lower for Trodelvy (9.6 months) compared to docetaxel (10.6 months).

Overall, more patients treated with Trodelvy were alive at the 12-month mark compared to those treated with docetaxel (46.6% vs. 36.7%).


In terms of safety, Grade ≥3 adverse events (AEs) were less common in the Trodelvy group (66.6%) compared to the docetaxel group (75.7%). Discontinuation due to AEs was also lower with Trodelvy (9.8%) versus docetaxel (16.7%). The most frequent AEs of any grade for Trodelvy included fatigue (57%), diarrhea (53%), and alopecia (43%), while for docetaxel, the common AEs were fatigue (56%), neutropenia (43%), and diarrhea (34%).

It's important to note that Trodelvy has not been approved by any regulatory body for the treatment of metastatic NSCLC, and its safety and efficacy for this indication have not been established. Trodelvy does carry a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea.


 

Pfizer’s LORBRENA CROWN Study Demonstrates Over Five Years of Progression-Free Survival in ALK-Positive Advanced Lung Cancer Patients

A remarkable 60% of patients are living without disease progression five years post-treatment

Updated data reveals an 81% reduction in the risk of progression or death and a 94% decrease in brain metastasis progression compared to XALKORI


Pfizer has released long-term follow-up results from the Phase 3 CROWN trial, which compares LORBRENA (lorlatinib, a third-generation ALK inhibitor, known in Europe as LORVIQUA) with XALKORI (crizotinib) in patients with previously untreated, ALK-positive advanced non-small cell lung cancer (NSCLC). After a median follow-up of five years, the median progression-free survival (PFS) for those on LORBRENA was not reached, showing a Hazard Ratio (HR) of 0.19, indicating an 81% reduction in the risk of disease progression or death compared to XALKORI. Additionally, 60% of patients on LORBRENA were progression-free at five years, compared to 8% of those on XALKORI.


This updated analysis also showed LORBRENA reducing the risk of intracranial (IC) progression by 94%. The median time to IC progression was not reached for LORBRENA patients, compared to 16.4 months (12.7-21.9) for those on XALKORI. Among patients without initial brain metastases, only 4 out of 114 on LORBRENA developed brain metastases within the first 16 months, compared to 39 out of 109 on XALKORI. At the time of analysis, 50% of patients in the CROWN trial were still receiving LORBRENA, while only 5% continued on XALKORI.


The safety profiles of LORBRENA and XALKORI over five years were consistent with prior reports, with no new safety concerns for LORBRENA. The most frequent adverse events (AEs) for LORBRENA, occurring in 20% or more of patients, were similar to the 2020 CROWN trial findings, including edema, weight gain, peripheral neuropathy, cognitive and mood effects, diarrhea, dyspnea, arthralgia, hypertension, headache, cough, fever, hypercholesterolemia, and hypertriglyceridemia. Grade 3/4 AEs were observed in 77% of LORBRENA patients and 57% of XALKORI patients. Treatment-related AEs resulted in permanent discontinuation for 5% of LORBRENA patients and 6% of XALKORI patients.


The CROWN trial is a Phase 3, randomized, open-label study involving 296 patients with previously untreated ALK-positive advanced NSCLC, divided equally to receive either LORBRENA (n=149) or XALKORI (n=147). The primary endpoint is PFS based on Blinded Independent Central Review (BICR), with secondary endpoints including PFS based on investigator assessment, overall survival (OS), objective response rate (ORR), intracranial objective response (IOR), and safety. Due to median PFS not being reached at three years, an unplanned post hoc analysis was conducted to evaluate long-term outcomes at the five-year mark.


LORBRENA is approved in the United States for treating adults with metastatic NSCLC that is ALK-positive, as detected by an FDA-approved test.


 

KRAZATI (adagrasib) Shows Notable Progression-Free Survival Improvement in Advanced or Metastatic KRASG12C-Mutated NSCLC Patients

Results from the Phase 3 KRYSTAL-12 trial, which evaluated KRAZATI (adagrasib) against standard chemotherapy in patients with locally advanced or metastatic KRASG12C-mutated non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy and anti-PD-(L)1 therapy, were recently announced. With a median follow-up period of 9.4 months, KRAZATI showed a statistically significant and clinically relevant enhancement in progression-free survival (PFS), the primary endpoint of the study, when compared to docetaxel, as determined by Blinded Independent Central Review (BICR).


The median PFS for KRAZATI was 5.5 months, while it was 3.8 months for docetaxel. Additionally, the overall response rate (ORR) assessed by BICR was significantly higher with KRAZATI than with docetaxel (32% vs. 9%). The median duration of response (mDOR) was 8.31 months for KRAZATI, compared to 5.36 months for docetaxel.


KRAZATI also showed a greater intracranial response rate in patients with baseline central nervous system (CNS) metastases, with a response rate per BICR more than double that seen with docetaxel (24% vs. 11%).

The KRYSTAL-12 trial is ongoing to evaluate the key secondary endpoint of overall survival.


No new safety concerns were identified for KRAZATI, and the safety data were in line with its known safety profile. Treatment-related adverse events (TRAEs) of any grade were observed in 94% of patients treated with KRAZATI and 86.4% of those treated with docetaxel. Grade ≥3 TRAEs were reported in 47% of KRAZATI patients and 46% of docetaxel patients.


 

Johnson & Johnson Announces Chemotherapy-Free Regimen of RYBREVANT Plus Lazertinib Shows Improved Progression-Free Survival in First-Line Treatment of High-Risk EGFR-Mutated NSCLC


  • New Data from Phase 3 MARIPOSA Study Highlights Benefits of RYBREVANT Combination for EGFR-Mutated Non-Small Cell Lung Cancer


Johnson & Johnson has released new data from the Phase 3 MARIPOSA study, which examined the use of RYBREVANT (amivantamab) in combination with lazertinib for first-line treatment of patients with high-risk epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The results demonstrated that this chemotherapy-free regimen significantly improved progression-free survival (PFS) compared to osimertinib in patients with EGFR exon 19 deletion (ex19del) or L858R mutations.


The MARIPOSA study included treatment-naïve patients with advanced EGFR-mutant (ex19del or L858R) NSCLC. The data revealed that RYBREVANT plus lazertinib significantly reduced the risk of disease progression or death when compared to osimertinib. High-risk features, such as brain or liver metastases, baseline TP53 co-mutations, and circulating tumor DNA (ctDNA) shedding, are prevalent in patients with advanced EGFR-mutated NSCLC and are linked to poor outcomes.


Notably, 89% of patients in the study had one or more of these high-risk characteristics at baseline, including 41% with brain metastases, 16% with liver metastases, 54% with TP53 co-mutations, 70% with ctDNA at baseline, and 15% who continued to shed ctDNA after two treatment cycles.


The analysis showed that treatment with RYBREVANT plus lazertinib significantly reduced the risk of disease progression or death across all high-risk subgroups:

  • A 31% reduction in patients with a history of brain metastases (18.3 vs. 13.0 months)

  • A 42% reduction in patients with baseline liver metastases (18.2 vs. 11.0 months)

  • A 35% reduction in patients with TP53 co-mutations (18.2 vs. 12.9 months)

  • A 32% reduction in patients with detectable ctDNA at baseline (20.3 vs. 14.8 months)

  • A 51% reduction in patients without cleared ctDNA at C3D1 (16.5 vs. 9.1 months)


Most adverse events (AEs) were Grade 1 or 2, and toxicity was generally manageable with dose interruptions, reductions, and supportive care. The most common Grade 3 or higher treatment-related AEs included rash and paronychia.


 

Initial Results from Phase 3 PALOMA-3 Study Reveal Five-Fold Reduction in Infusion-Related Reactions with Five-Minute Subcutaneous Amivantamab Administration

Johnson & Johnson has released the first data from the Phase 3 PALOMA-3 study, which investigated subcutaneous (SC) administration of amivantamab in combination with lazertinib for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletion (ex19del) or L858R mutations. The study found that the efficacy and pharmacokinetics of SC amivantamab combined with lazertinib were non-inferior to the intravenous (IV) formulation of RYBREVANT (amivantamab-vmjw), the currently approved version.


Significantly, the SC amivantamab administration time was reduced to about five minutes compared to the five-hour IV process spread over two days, and it resulted in a five-fold decrease in infusion-related reactions (IRRs).


The study results confirmed that SC amivantamab was non-inferior to its IV counterpart, meeting the co-primary pharmacokinetic efficacy endpoints based on amivantamab blood levels (Ctrough and area under the serum concentration-time curve from day 1 to 15).


With a median follow-up of seven months, the overall response rate was 30% in the SC group and 33% in the IV group, satisfying the criteria for non-inferiority. SC amivantamab also exhibited longer duration of response (DoR), progression-free survival (PFS), and significantly better overall survival (OS) compared to the IV formulation during this period.


Specifically, the median DoR was 11.2 months for SC amivantamab with lazertinib versus 8.3 months for IV, and the median PFS was 6.1 months compared to 4.3 months. A pre-specified exploratory analysis indicated significantly longer OS for patients receiving SC amivantamab. After 12 months, 65% of patients on the SC regimen were alive versus 51% on the IV regimen. It is suggested that the efficacy of SC amivantamab may be due to its absorption via the lymphatic system, potentially enhancing immune-mediated effects.


Importantly, the administration time for SC amivantamab was much shorter (median less than five minutes) compared to the IV method (up to five hours), and a higher percentage of patients found the SC administration more convenient (85% vs 35% at the end of treatment).


The safety profile of SC amivantamab was consistent with the known safety profile of the IV administration. The most common all-grade adverse events (≥ 20%) for SC versus IV administration were paronychia (54% vs 51%), hypoalbuminemia (47% vs 37%), and rash (46% vs 43%). No Grade 4 or 5 IRRs were reported.


 

Imfinzi First to Show Survival Benefit in Limited-Stage Small Cell Lung Cancer in Global Phase III Trial, Cutting Death Risk by 27% Compared to Placebo

  • In the ADRIATIC Phase III trial, 57% of patients treated with Imfinzi were alive after three years.

  • Positive findings from the ADRIATIC Phase III trial demonstrated that AstraZeneca’s Imfinzi (durvalumab) significantly improved both overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed after standard concurrent chemoradiotherapy (cCRT), compared to placebo.


The interim analysis showed that Imfinzi decreased the risk of death by 27% compared to placebo. The median OS was 55.9 months for the Imfinzi group versus 33.4 months for the placebo group. Three years into treatment, 57% of patients receiving Imfinzi were still alive, compared to 48% of those on placebo. Additionally, Imfinzi reduced the risk of disease progression or death by 24% compared to placebo. The median PFS was 16.6 months for Imfinzi and 9.2 months for placebo. At two years, 46% of patients on Imfinzi had not experienced disease progression, compared to 34% of patients on placebo.


The benefits in OS and PFS were consistent across various key prespecified patient subgroups, including age, sex, race, disease stage at diagnosis, prior radiation, and whether prophylactic cranial irradiation was administered.


Key Results:

  • Median OS: Imfinzi vs. placebo: 55.9 vs. 33.4 months

  • OS Rate at 24 Months: Imfinzi vs. placebo: 68.0% vs. 58.6%

  • Median PFS: Imfinzi vs. placebo: 16.6 vs. 9.2 months

  • PFS at 24 Months: Imfinzi vs. placebo: 46.2% vs. 34.2%



 

Blenrep Combination Significantly Lowers Disease Progression or Death Risk by Nearly 50% in Relapsed/Refractory Multiple Myeloma

GlaxoSmithKline (GSK) has unveiled promising interim findings from the DREAMM-8 Phase III trial, which assessed the efficacy of Blenrep (belantamab mafodotin) combined with pomalidomide and dexamethasone (PomDex) against a standard treatment regimen of bortezomib plus PomDex for patients with relapsed or refractory multiple myeloma.


The trial demonstrated a statistically significant and clinically meaningful enhancement in progression-free survival (PFS) with the Blenrep combination. Specifically, the hazard ratio (HR) was 0.52, indicating a nearly 50% reduction in the risk of disease progression or death compared to the bortezomib combination. At a median follow-up of 21.8 months, the median PFS for the Blenrep group had not been reached, in contrast to 12.7 months for the bortezomib group. After one year, 71% of patients receiving the Blenrep combination were alive and had not experienced disease progression, compared to 51% in the bortezomib group.


belantamab mafodotin + pomalidomide and dexamethasone

pomalidomide + bortezomib and dexamethasone

ORR (overall response rate)

77%

72%

CR or better rate

40%

16%

Duration of response

Not reached

17.5 months

VGPR or better rate

64%

38%



This benefit was consistent across all pre-specified subgroups, including those with poor prognostic indicators such as lenalidomide-refractory patients and those with high-risk cytogenetics.


While the interim analysis indicated a positive trend in overall survival (OS) with an HR of 0.77, this result was not statistically significant. OS follow-up is ongoing, with further analyses planned. At one year, the survival rate was 83% for the Blenrep combination group compared to 76% for the bortezomib group.


The safety profile of the Blenrep combination was generally consistent with the known effects of the individual drugs. This Phase III trial marks the second instance of robust efficacy for a Blenrep combination therapy compared to a standard care regimen in second-line and later treatment settings for relapsed/refractory multiple myeloma.

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