1. Abstract Number – LBA7005

Title: Pfizer is all set to present data from an ECHELON-3 trial for its antibody-drug conjugate ADCETRIS, potentially supporting a future regulatory filing in DLBCL

Commentary - The combination of ADCETRIS with REVLIMID and RITUXAN led to a significant improvement in overall survival. The final results will be showcased during ASCO conference.

Executive Summary – Brief data from the ECHELON-3 trial in March 2024 showed that ADCETRIS combined with lenalidomide and rituximab significantly improved overall survival, progression-free survival, and overall response rate compared to lenalidomide and rituximab plus placebo, regardless of CD30 expression. Pfizer is set to present the final findings at the upcoming ASCO conference.

Main Content – ADCETRIS is comprised of an anti-CD30 monoclonal antibody that is attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE). The antibody-drug conjugate (ADC) was acquired by Pfizer when it completed its USD 43 billion deal for Seagen in December 2023.

In March 2024, Pfizer announced that the Phase III study, ECHELON-3, of ADCETRIS in combination with lenalidomide and rituximab for the treatment of patients with relapsed/refractory DLBCL showed a statistically significant and clinically meaningful improvement in overall survival (OS) compared to lenalidomide and rituximab plus placebo. Positive outcomes were also observed in key secondary endpoints. The safety and tolerability of ADCETRIS in the ECHELON-3 trial were consistent with what has been previously presented for patients with relapsed/refractory DLBCL treated with ADCETRIS in clinical trials.

Pfizer intends to present the full data at the upcoming ASCO meeting and submit it to the US FDA to potentially support a regulatory filing in the US.

Conclusion: ADCETRIS has already been approved for seven indications in the US, and this approval could pave the way for an eighth. However, the initial patent expiry of ADCETRIS in the US in 2024 is expected to lead to stagnation in this currently growing market.

2. Abstract Number – LBA6500

Title: Novartis will highlight the primary analysis from the pivotal Phase III ASC4FIRST trial, with planned submission of SCEMBLIX in 2024 for 1L CML

Commentary – Novartis looks forward to sharing the primary analysis from the pivotal Phase III ASC4FIRST trial, which builds on our over 20-year legacy to transform care for people diagnosed with CML.

Executive Summary – The primary results from ASC4FIRST, a pivotal Phase III study of SCEMBLIX versus standard-of-care tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, and bosutinib) in newly diagnosed patients with Ph+ CML-CP will be shared by Novartis at the ASCO official Press Program.

Main Content –  SCEMBLIX (asciminib) is the first FDA-approved CML treatment that binds to the ABL myristoyl pocket. In October 2021, the FDA granted accelerated approval to SCEMBLIX for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, previously treated with two or more tyrosine kinase inhibitors, and approved asciminib for adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with the T315I mutation.

The ASC4FIRST Phase III study (NCT04971226) evaluates SCEMBLIX as a first-line treatment in CML. As per Novartis Q1 2024, earnings call transcript, primary endpoints were met versus all standard of care TKI and -- versus GLEEVEC as well, favorable safety and tolerability profile. Novartis will be presenting the full data at the ASCO 2024 meeting.

SCEMBLIX saw an 83% growth in Q1 2024, primarily driven by its third-line indication. With the first-line submission on track to be completed in the coming months based on the ASC4FIRST Phase III study, the product is expected to continue experiencing strong demand.

Conclusion: The primary endpoint of the ASC4FIRST study was the major molecular response (MMR), making it intriguing to see how SCEMBLIX performs in this regard. One exciting aspect of SCEMBLIX is its long exclusivity period, and because it targets a rare disease, it is not subject to negotiations with the IRA. This positions Novartis to experience growth with SCEMBLIX throughout this decade and well into the next, both in the US and globally.

3. Abstract Number – LBA105

Title: GSK is set to unveil pivotal data from the DREAMM-8 Phase III trials showing the potential of belantamab mafodotin in multiple myeloma

Commentary – DREAMM-8 results for BLENREP in multiple myeloma will be featured in a late-breaking presentation and ASCO’s Press Programme

Executive Summary –  BLENREP, in combination with pomalidomide plus dexamethasone (PomDex), meets its PFS at a pre-specified interim analysis, detailed findings from the DREAMM-8 trial will be presented at the upcoming ASCO 2024. 

Main Content –  BLENREP is an antibody-drug conjugate comprising a humanized B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen. 

In 2022, GSK decided to pull BLENREP from the US market after its DREAMM-3 trial failed to reach the primary goal. 

Positive news came in 2024, when GSK announced positive headline results from a planned interim analysis of the DREAMM-8 Phase III head-to-head trial evaluating belantamab mafodotin, in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex, as a second line and later treatment for relapsed or refractory multiple myeloma. The trial met its primary endpoint of PFS, with the belantamab mafodotin combination significantly extending the time to disease progression or death versus the standard of care combination. A positive OS trend favoring the belantamab mafodotin combination was also observed at the time of this analysis. The trial continues to follow up for OS.

Positive findings from DREAMM-7, a Phase III head-to-head trial evaluating belantamab mafodotin in combination with bortezomib and dexamethasone (BorDex) versus daratumumab plus BorDex in the same treatment setting, were presented at the American Society of Clinical Oncology (ASCO) Plenary Series on 6th February 2024.

Results from DREAMM-8 will be presented at ASCO 2024 and data from both DREAMM-7 and DREAMM-8 are being shared with health authorities.

Conclusion: Regulatory decision (US, EU, JP) based on DREAMM-7/8 trial in 2L+ multiple myeloma and regulatory submission (CN) based on DREAMM-8 trial in 2L+ multiple myeloma planned in 2025. If approved, these combinations have the potential to redefine the treatment of relapsed or refractory multiple myeloma and advance the standard of care.

4. Abstract Number – LBA7003

Title: Chidamide plus R-CHOP approved in China for MYC/BCL2–expressing DLBCL findings from pivotal trial to be disclosed at ASCO 2024 

Commentary – Findings from the Phase III DEB trial (NCT04231448) which led to the approval of EPIDAZA (chidamide) for treatment of previously untreated DLBCL with positive MYC and BCL2 expression in China to be covered at the upcoming conference.

Executive Summary –  Ahead of the American Society of Clinical Oncology annual meeting, Shenzhen Chipscreen Biosciences announced that the company's lead innovative product EPIDAZA (chidamide), has been officially approved by the National Medical Products Administration (NMPA), more on the results will be presented as late-breaking abstract during the 2024 ASCO Annual Meeting. 

Main Content –  EPIDAZA (chidamide/tucidinostat), a Class 1.1 innovative drug, is a novel molecular entity with global patent protection and the first marketed product developed independently by Chipscreen Biosciences. The first original chemical new drug approved in China, Chidamide is also the first oral subtype-selective histone deacetylase (HDAC) inhibitor in the world, Since its approval in China in December 2014 for the treatment of peripheral T-cell lymphoma, Chidamide has achieved significant commercialization worldwide and continuously explored new indications.

In April 2024, Shenzhen Chipscreen Biosciences announced that the company's lead innovative product Chidamide, combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), has been officially approved by the National Medical Products Administration (NMPA) for treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) with positive MYC and BCL2 expression. 

This regulatory decision was supported by interim findings from the Phase III DEB trial (NCT04231448), which confirmed that the efficacy and safety indicators set by the protocol were achieved. A trend toward improved event-free survival, the trial’s primary endpoint, was also observed with the chidamide combination vs R-CHOP alone. Regarding safety, the chidamide combination’s toxicity profile is consistent with known risks, and no new significant safety signals were observed. The company quoted that these results will be presented as a late-breaking abstract during the 2024 ASCO Annual Meeting.

Conclusion: The R-CHOP regimen has been a standard first-line treatment for DLBCL for almost two decades, but its effectiveness is limited in patients with dual expression of BCL-2 and MYC proteins. To address this, the combination of chidamide and R-CHOP is being studied in the world's first Phase III registered clinical trial focused on first-line therapy for dual-expressed DLBCL. This study represents the first attempt to enhance the efficacy of R-CHOP and has shown significant benefits in achieving complete remission. The approval is expected to bring new hope and improved survival outcomes to patients with DLBCL.