ASCO highlights


ASCO highlights

Published: Jun 06, 2023

By BioSpace Editorial Staff

The American Society of Clinical Oncology 2023 annual meeting kicked off Friday in Chicago, and BioSpace’s Greg Slabodkin spoke with leading biopharma analysts about the most-anticipated ASCO abstracts.

Keep checking back for more ASCO highlights.

June 5: Monday, Merck and Moderna presented data from the Phase IIb KEYNOTE-942 trial of mRNA-4157, showing that the mRNA-based vaccine in combination with Keytruda reduced the risk of spread to other organs or death in high-risk melanoma by 65%.

Distant metastasis-free survival (DMFS)—defined as time from the first dose of Keytruda until the first distant recurrence or death from any cause—was a key secondary endpoint of the trial. The ASCO data reveal followed the April announcement that the combo reduced the risk of cancer recurrence or death by 44% compared to Keytruda alone. These results were presented at the American Association for Cancer Research (AACR) annual meeting, also in April. 

“Patients who experience metastases at distant sites typically have worse survival outcomes and a poor prognosis,” Kyle Holen, senior vice president and head of development, therapeutics and oncology at Moderna, said in a prepared statement, adding that the results “underscore” the potential of neoantigen therapy, a type of personalized vaccine.  

The companies plan to begin a Phase III trial in melanoma later in 2023, according to the press release.

 June 5: Monday morning, Johnson & Johnson’s Janssen Pharmaceutical and Legend Biotech announced their CAR T-cell therapy, Carvykti (ciltacabtagene autoleucel), reduced the risk of disease progression or death by 74% in multiple myeloma patients compared to two standard of care treatment regimens.

In doing so, the companies confirmed data from an abstract that was inadvertently posted online  in April that showed Carvykti, a BCMA-targeting CAR T-cell therapy, reduced the risk of disease progression or death in multiple myeloma by 74%.

The Phase III trial, dubbed CARTITUDE-4, enrolled 419 multiple myeloma patients who did not respond to Revlimid (lenalidomide), a maintenance therapy developed by Bristol Myers Squibb. Some patients had also received either one or two additional treatments in the past. The positive data means that instead of being used only after several treatments have tried and failed, Carvykti could now potentially be administered after only Revlimid is shown to be ineffective.

Notably, 99% of patients (175 out of 176) who were treated with Carvykti responded to treatment, meaning their blood cancer counts were lowered.

“Ciltacabtagene autoleucel has not only shown that it delivers remarkably effective outcomes compared to patients’ current options, but also that it can be used safely earlier in the treatment phase,” said Oreofe Odejide, a medical oncologist at Dana-Farber Cancer Institute, in an ASCO press release.

In March 2022, J&J and Legend received approval from the FDA for Carvykti to treat multiple myeloma. Last month, Janssen submitted a Type II variation application to the European Medicines Agency based on the CARTITUDE-4 study results seeking approval of Carvykti for the earlier treatment of patients with relapsed and lenalidomide-refractory multiple myeloma. 

June 5: Partners AstraZeneca and Daiichi Sankyo presented positive data Monday from two Phase II trials of Enhertu (trastuzumab deruxtecan) in a range of HER2 expressing advanced solid tumors, including metastatic colorectal cancer.  

In the DESTINY-PanTumor02 Phase II trial, Enhertu led to a 37.1% objective response rate (ORR) in the overall trial population, the companies said in separate press releases. The trial studied Enhertu, a HER2-directed antibody-drug conjugate (ADC), as a third-line treatment for patients with HER2-expressing advanced solid tumors, including biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers. Patients whose tumors had the highest level of HER2 expression saw an ORR of 61.3%, which was confirmed by central testing.  

A complete response was seen in 15 patients, while 84 patients had partial responses. Nearly half the patients who had a response maintained the response at one year, the companies reported.  

In the DESTINY-CRC02 Phase II trial, patients with HER2-positive metastatic colorectal cancer saw ORRs of 37.8% and 27.5% from treatment with Enhertu 5.4mg/kg and 6.4mg/kg, respectively. All responses—which were assessed by blinded independent central review (BICR)—were partial. Again, patients whose tumors expressed the highest levels of HER2 saw the best outcomes.  

June 4: Servier Pharmaceuticals saw its $1.8 billion acquisition of Agios Pharmaceuticals’ oncology business validated as vorasidenib, a key asset in the deal, showed positive results in a pivotal grade 2 glioma trial. 

Servier presented the results, the likes of which trial investigator Katherine Peters said haven’t been seen in 20 years, at ASCO on Sunday.

June 4Seagen is facing stiff competition in advanced Hodgkin’s lymphoma after Bristol Myers Squibb’s Opdivo (nivolumab) bested its Adcetris (brentuximab vedotinb) in a head-to-head Phase III trial. The data were presented Sunday at ASCO.

The trial consisted of 976 people 12 and above with previously untreated disease. See here for full details. 

June 3: In the Phase III KEYNOTE-671 trial, perioperative treatment with Merck‘s Keytruda (pembrolizumab) plus chemotherapy emerged as a superior option to pre-operative chemotherapy in terms of event-free survival (EFS) for patients with resectable stage II, IIIA or IIIB NSCLC.

After 25 months, treatment with the Keytruda regimen reduced the risk of disease recurrence, progression or death by 42%, according to a press release issued Saturday by Merck.

The results are significant both for patients—lung cancer is the leading cause of death globally, with NSCLC making up about 81% of cases, according to Merck—and for Merck itself, as they trump those of competitor AstraZeneca, whose Phase III trial saw a 32% EFS in this indication. See here for more details on one of ASCO’s most highly-anticipated readouts.

June 2: In March, BioNTech dropped $200 million upfront for exclusive global rights to OncoC4’s anti-CTLA-4 monoclonal antibody candidate, ONC-392. On Friday, the development partners reported positive early data to be presented at ASCO from a Phase I/II trial studying the drug—now BNT316/ONC-392—in metastatic, PD-(L)1-resistant non-small cell lung cancer (NSCLC). 

Data from 27 patients showed an overall response rate of 29.6% and a disease control rate of 70.4%. One patient had a complete response, seven saw a partial response and 11 patients had stable disease. BioNTech and OncoC4 called the safety profile “manageable” with Grade 3 or 4 Immune-related adverse events occurring in 10 patients.  

“Responses were observed regardless of PD-L1 status, and among those who failed multiple lines of immunotherapy and chemotherapy, including PD-1 and CTLA-4 combination therapy,” Pan Zheng, chief medical officer and co-founder at OncoC4, said in a prepared statement.   

A pivotal Phase III trial is expected to begin in the third quarter of 2023, according to the press release.  

June 2: Novartis presented early data from a Phase III trial of Kisqali (ribociclib) in HR-positive HER2-negative early-stage breast cancer. The addition of Kisqali in the adjuvant setting reduced patients’ risk for recurrence by 25% compared to those on the endocrine therapy alone.

Source BioSpace