Following up on the recent American Society of Clinical Oncology annual meeting, held 31 May-4 June in Chicago, Datamonitor Healthcare senior analyst Flora Mackay and Citeline senior analyst David Dahan reviewed some of the data highlights and offered insight into how it will shape the future of oncology.
Neoadjuvant Therapy For Melanoma:
A couple of trials were featured exploring the use of neoadjuvant, or pre-surgical, treatment of melanoma. “For melanoma patients surgery is still undertaken with curative intent, so you don’t want to run the risk of using a neoadjuvant therapy which causes surgery-delaying side effects and the patient missing an opportunity for curative resection,” Mackay said.
Standard of care is using a PD-1 inhibitor as adjuvant (post-surgical) treatment, with Bristol Myers Squibb Company’s Opdivo and Merck & Co., Inc.’s Keytruda both approved in that setting. The drugs offer a significant improvement in relapse-free survival and long-term survival, but can cause immune-related adverse events. Safety was an important factor for the early treatment setting, Mackay explained.
She reviewed both the safety and efficacy findings from two trials in neoadjuvant treatment of melanoma: the Phase III PIVOTAL trial of Sun Pharmaceuticals/Philogen’s Nidlegy (intralesional daromun) and the open-label Phase III NADINA trial comparing use of BMS’s Opdivo plus Yervoy as neoadjuvant treatment of Stage III melanoma against standard adjuvant treatment with Opdivo.
Chronic Myeloid Leukemia (CML):
The Phase III ASC4FIRST trial investigated Novartis AG’s Scemblix (asciminib) as frontline therapy for chronic phase CML patients, which Mackay explained could emerge as the most potent tyrosine kinase inhibitor (TKI) for frontline use, but just before generic entry for several of the second-generation TKIs.
Multiple Myeloma:
In multiple myeloma, Dahan highlighted a pair of pivotal Phase III trials that could help return GSK plc’s anti-BCMA antibody-drug conjugate Blenrep to the market. Belantamab mafodotin received FDA accelerated approval for fifth-line or later MM and EU approval for fourth-line or later disease in 2020, but Blenrep was removed from both markets after the failure of the DREAMM-3 confirmatory trial.
Two other trials in GSK’s program have subsequently succeeded in an earlier line of treatment and the Phase III DREAMM-7 and DREAMM-8 trials were both presented at ASCO 2024. DREAMM-7 evaluated Blenrep combined with Velcade and dexamethasone while DREAMM-8 evaluated Blenrep combined with Pomalyst and dexamethasone, both as second-line or later treatment.
“Looking at these results what is impressive is the improvement in deep responses. In both trials we see a doubling or near doubling of the complete response or better rate which includes both complete responses and stringent responses,” Dahan said.
Breast Cancer:
Daiichi Sankyo Co., Ltd./AstraZeneca PLC’s HER2-directed ADC Enhertu (trastuzumab deruxtecan) was studied in hormone-receptor positive, HER2-negative breast cancer in the Phase IIIDESTINY-Breast06 trial inHER2-low and HER2-ultralow metastatic breast cancer patients who had progressed on one or more lines of endocrine therapy.
“Enhertu has already demonstrated efficacy in the Phase III Destiny-Breast04 trial which enrolled HER2-low patients who have progressed on prior lines of chemotherapy,” Dahan said, and has been approved for this setting. The difference in DESTINY-Breast06 is that “it enrolled chemotherapy-naïve patients as well as HER2-ultralow patients, which accounts for approximately 20-25% of the hormone receptor positive breast cancer population.” Dahan reported that Enhertu yielded “impressive” results in both HER2-low and ultralow populations in DESTINY-Breast06 and reviewed subgroup analyses and the competitive landscape for this setting as well.
Prostate Cancer:
Radioligand therapy is becoming increasingly popular in metastatic castration-resistant prostate cancer, Mackay explained, reviewing first-in-human results for Johnson & Johnson’s human kallikrein-related peptidase 2 (hK2) targeting radioligand from a Phase I trial of JNJ-69086420, which delivers the high-energy alpha particle emitter actinium-255 to prostate cancer cells. Mackay explained the current radiotherapy market is split between alpha and beta-emitting radioconjugates and how J&J’s new radioligand could fit into that market.
The drug showed promising efficacy but larger trials will be needed to see whether the benefit can mitigate treatment-related adverse events, she said.
ALK+ NSCLC:
Mackay pointed out some long-term data from the Phase III CROWN study of Pfizer Inc.’s Lorbrena (lorlatinib) in non-small cell lung cancer patients with an ALK mutation that could help resolve questions about first-line use. “In these updated data from CROWN, Lorebrena’s efficacy continues to look impressive with median progression free survival still not reached after five years follow up. Moreover, 60% of patients treated with Lorbrena are alive without disease progression vs 8% in the Xalkori comparator arm,” she reported.
Mackay looked at the data in the context of the continuing debate over what line of therapy Lorbrena should be used, either reserved for hard-to-treat patients or as a “big gun” in the frontline.
Hepatocellular Carcinoma:
The landscape of first-line treatments for HCC is complicated, Dahan explained, with kinase inhibitors up against Roche’s Tecentriq/Avastin and multiple checkpoint inhibitor combinations in development. He looked at Phase III data from both the CheckMate-9DW study of Opdivo plus Yervoy and updated data from the CARES-310 trial of Elevar Therapeutics/Jiangsu’s anti-PD-1 camrelizumab plus angiogenesis inhibitor rivoceranib, both of which have the potential to replace the current standard of care.
Bladder Cancer:
Non-invasive bladder cancer represents about 70%-75% of bladder cancers and is treated primarily with the bacillus calmette Guerin (BCG) vaccine, though in more than half of cases that treatment fails. Currently these unresponsive patients are treated with Keytruda or more recently the adenoviral vector-based gene therapy Adstiladrin and recombinant immunocytokine Anktiva.
Dahan compared the existing Keytruda data against the single-arm Phase II CORE-001 trial of CG Oncology’s oncolytic immunotherapy cretostimogene in combination with Keytruda in BCG-unresponsive high-risk NMIBC, which he said “bodes well” for the combination’s prospects.
Acute Myeloid Leukemia:
The open-label Phase II BP1001-201 trial is investigating the safety and efficacy of Bio-Path’s liposomal-incorporated Grb2 antisense oligonucleotide prexigebersen in frontline adverse-risk secondary and relapsed/refractory AML. The trial compared prexigerbersen + decitabine + Venclexta versus historical decitabine + Venclexta in patients ineligible to receive intensive chemotherapy.
The Phase II trial is ongoing, but Mackay noted a Phase III trial will need to show superior efficacy to the Venclexta/azacitidine or Venclexta/decitabine combination. “Given the interim data, however, we reasonably expect that despite the high approval bar, prexigebersen may still carve about a niche in the AML market,” she said.
