Moderna, Revolution Medicines and Zymeworks record wins in melanoma, lung and breast cancers, while BeOne swings and misses at head and neck cancer.
The American Association for Cancer Research annual meeting is in full swing, featuring some of the latest developments in biopharma’s most dynamic therapeutic area. Experts from all over the world have congregated in the San Diego Convention Center to present cutting-edge research that could push the field forward and potentially change clinical practice.
BioSpace rounds up some of the most interesting presentations here.
Moderna presents “competitive” first-line data for melanoma antigen therapy
Moderna’s investigational antigen therapy mRNA-4359, when used alongside Merck’s anti-PD-1 blockbuster Keytruda, elicited an 83% overall response rate (ORR) in patients with locally advanced or metastatic melanoma who hadn’t been exposed to prior treatments.
Two patients in the Phase 1/2 study achieved a complete response (CR)—the total absence of any signs of remaining cancer—while eight experienced partial responses, according to an oral presentation at AACR. Disease control rate hit 92%.
“The encouraging data looks competitive to approved 1L options offering a differentiated off-the shelf-approach,” Jefferies analysts told investors in a Monday note.
In terms of competition, the firm pointed to Bristol Myers Squibb’s Opdualag—a combination of the anti-LAG-3 antibody relatlimab and the pharma’s PD-1 blocker Opdivo—which according to its label generated an ORR of 43% and a CR of 16%. Opdualag was approved in 2022 for unresectable or metastatic melanoma. Jefferies also referred to Regeneron’s Libtayo plus fianlimab, a combo regimen that in a Phase 2 study demonstrated an ORR of 57%.
MRNA-4359 plus Keytruda has been granted the FDA’s fast track designation for unresectable or metastatic melanoma, Moderna said in a news release on Friday. The company “is targeting a potential drug launch by 2028,” Jefferies added in its note.
Revolution updates lung cancer data after epic pancreatic cancer win
Following its knockout late-stage victory in pancreatic cancer, Revolution Medicines presented a detailed breakdown of Phase 1 data for its lung cancer drug zoldonrasib at AACR.
The results showed a 52% confirmed ORR with a 93% disease control rate. This outcome “decreased slightly” from a prior readout, analysts at Leerink Partners told investors in a Monday note, pointing to an April 2025 readout that showed a 61% ORR. “This data cut included more patients,” Leerink said by way of an explanation, “and a longer follow-up time.”
The study, dubbed RMC-9805-001, also found that median progression-free survival (PFS) reached 11.1 months, with 48% of patients being free of disease progression at 12 months. Overall survival rate were not yet mature by the time of the AACR readout, but the study hit an estimated survival rate of 73% at 12 months, “suggesting encouraging early survival outcomes,” according to a Monday press announcement.
Zoldonrasib is a tri-complex inhibitor that works by binding to and creating a complex with cyclophilin A, in turn selectively blocking the active form of a certain cancer-causing RAS mutant. Around 29% of all RAS cancers are linked to this specific genetic anomaly, according to Revolution’s release, with no approved targeted therapy. Aside from lung cancer, the biotech is also studying zoldonrasib in pancreatic cancer and other solid tumors.
‘Encouraging’ win for Zymeworks, BeOne and Jazz’s bispecific backs cutting chemo in early breast cancer
A neoadjuvant course of Zymeworks’ bispecific antibody zanidatamab can help minimize or eliminate the need for chemotherapy in patients with early-stage HER2-positive breast cancer.
“Strategies are needed to de-escalate treatment” in these patients, according to the abstract of an investigator-initiated trial presented at AACR. At six weeks, zanidatamab treatment before surgery significantly reduced tumor size and volume, as measured by ultrasound and magnetic resonance imaging.
Six patients achieved a pathologic complete response, while four had limited residual cancer burden.
These results are “encouraging but early,” Leerink analysts wrote on Monday, noting that zanidatamab’s activity “appeared enriched in patients with HER2+” tumors. Zymeworks is advancing zanidatamab along with BeOne Medicines and Jazz Pharmaceuticals for a variety of malignancies, including gastroesophageal adenocarcinoma, biliary tract cancer and different types of breast cancer.
Zanidatamab is a bispecific antibody that targets two sites on the HER2 protein. This mechanism of action facilitates the immune system’s anticancer response, in turn preventing the tumor’s growth and triggering its death. The drug was approved by the FDA in 2024 for unresectable or metastatic HER2-positive biliary tract cancer, for which it is marketed as Ziihera.
BeOne’s experimental Tevimbra combos show no added benefit over PD-1 monotherapy
BeOne is proposing a clutch of cancer combination regimens based on its PD-1 inhibitor Tevimbra—but data presented at AACR did not show improved efficacy over monotherapy.
In a Phase 2 study, BeOne combined Tevimbra with the anti-TIM-3 antibody surzebiclimab and/or the anti-LAG-3 therapy alcestobart. The biotech treated 160 patients with recurrent and/or metastatic head and neck squamous cell carcinoma.
Over a median follow-up of 13.1 months, ORR reached 27.5% in patients on Tevimbra plus surzebiclimab and those given all three therapies. Participants on Tevimbra plus alcestobart had an ORR of 25%. Meanwhile, Tevimbra monotherapy yielded an ORR of 27.5%—not significantly different than the three investigational arms.
Clinical benefit rate and disease control rate were likewise comparable across all four study groups.
While the combo arms didn’t show added benefit over Tevimbra monotherapy, the discussant during the data presentation “did point out that this was a heterogenous population and there might be more benefit in the PD-L1 low tumors,” Leerink Partners wrote in an investor note on Monday.
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