ESMO 2022: AstraZeneca, Regeneron, GRAIL and More

2022-09-12

细胞疗法

Monday morning’s ESMO 2022 update brings news of a robust Keytruda/Padcev combination, positive data from Regeneron regarding Libtayo in cutaneous squamous cell carcinoma (CSCC) and hopeful news from an early detection cancer test from GRAIL. Astellas, Seagen and Merck Score in Urothelial Cancer Astellas and Seagen’s Padcev (enfortumab vedotin-ejfv) in combination with Merck’s Keytruda in metastatic urothelial cancer (Ia/mUC) demonstrated a 64.5% confirmed objective response rate (ORR), the companies reported Monday. The Phase Ib/II trial cohort K met the primary endpoint. Of the participants assessed, 10.5% achieved a complete response and 53.9% demonstrated a partial response. The median duration of response (DOR) per BICR was not reached. In a monotherapy arm assessing Padcev monotherapy as first-line treatment for the same indication, data demonstrated a 45.2% confirmed ORR. The monotherapy arm was not designed to be compared to the combination arm. Jonathan E. Rosenberg, M.D., chief of genitourinary medical oncology service, division of solid tumor oncology at Memorial Sloan Kettering and Cohort K primary investigator, said the results “support the ongoing investigation of enfortumab vedotin and pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer.” Libtayo Combo Appears Promising in Neoadjuvant CSCC Among 16 presentations at ESMO, Regeneron announced positive clinical data from a combination therapy of Libtayo (cemiplimab) as neoadjuvant monotherapy in stage II to IV resectable CSCC. The data, from the primary analysis of a confirmatory Phase II trial, was also published in the New England Journal of Medicine. In the Phase II trial, 79 patients received up to four fixed doses of Libtayo every three weeks before surgery. 62 received all four doses and 70 underwent surgery. Of these participants, 63.3% had a combined pathologic response rate, with 50.6% achieving the primary endpoint of complete pathologic response and 12.7% demonstrating a major pathologic response by independent pathologic review. There was a 68% objective response rate (ORR) with 5 complete responses and 49 partial responses per local imaging review. “This is exactly what our broad pipeline is trying to do,” using a variety of approaches to turn “cold tumors” into “hot tumors,” David Weinreich, M.D., EVP, global clinical development at Regeneron, said in a Monday webcast. GRAIL’s Galleri More than Doubles Cancers Detected GRAIL’s Galleri multi-cancer early detection (MCED) screening blood test added to standard of care screening more than doubled the number of cancers detected compared to standard screening alone, the company announced Monday. GRAIL’s Galleri assay “detected more cancers than all U.S. Preventive Services Task Force-recommended standard single cancer screenings combined,” Jeffrey Venstrom, M.D., chief medical officer at GRAIL, said in a statement. These included Stage I cancers of the liver, small intestine and uterus, and Stage II pancreatic, bone and oropharyngeal cancers. “This is particularly notable given the PATHFINDER population was heavily screened with higher-than-average rates for mammography, colonoscopy and low-dose CT lung scans,” Venstrom added. AstraZeneca Touts Impressive Long-term Data in NSCLC Four-year follow-up data from AstraZeneca’s Phase III trial of tremelimumab plus Imfinzi (durvalumab) showed a sustained improvement in OS compared to chemotherapy alone in first-line treatment of Stage IV metastatic non-small cell lung cancer (NSCLC). The combination was added to four cycles of chemotherapy. Further analysis showed an OS improvement trend for the combination in cancer-specific mutations, including STK11, KEAP1 and KRAS-mutated MSCLC and PD-L1-negative tumors PD-L1-negative tumors. “These results support the addition of a limited course of tremelimumab to durvalumab plus chemotherapy as a potential new treatment option for patients with these harder-to-treat forms of lung cancer,” stated Melissa Johnson, M.D., director of Lung Cancer Research Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology and lead investigator of the POSEIDON trial. AstraZeneca also announced that Tagrisso (osimertinib) led to 5.5-year median disease-free survival in patients with early-stage EGFR-mutated NSCLC when dosed in the adjuvant setting. The data, from the Phase III ADAURA trial, showed Tagrisso decreased risk of disease recurrence or death by 77% in the primary analysis population and by 73% in the overall trial population. Jiangsu Hengrui Reports “Significantly Prolonged OS” in uHCC Jiangsu Hengrui Pharmaceuticals Co.reported that camrelizumab, an anti-PD1 checkpoint inhibitor, combined with rivoceranib (apatinib), significantly prolonged OS and progression-free survival (PFS), with improved ORR versus sorafenib in first-line unresectable hepatocellular carcinoma (uHCC). Median OS was 22.1 months compared to 15.2 months with sorafenib alone. The median PFS for the combination was 5.6 months compared to 3.7 months for standard of care sorafenib. And confirmed ORR for the combination was 25.4% compared to 5.9% for sorafenib. Lyell Presents Trial Design FOR CAR T-cell Therapy Lyell Immunopharma announced a poster of its first-in-human Phase I trial design for LYL797. The drug is an ROR1-targeted CAR T-cell therapy for the treatment of solid tumors. It is specifically targeting patients with receptor tyrosine kinase-like orphan receptor 1-positive (ROR1+) solid tumors ROR1+) solid tumors. LYL797 uses both Gen-R and Epi-R, Lyell’s novel reprogramming technologies engineered to overcome barriers to successful adoptive cell therapy, such as T-cell exhaustion and lack of durable stemness. The trial will evaluate the drug in patients with relapsed/refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). "We look forward to testing our technology platforms in the clinic, thus specifically addressing the question of exhaustion and durable stemness as barriers to successful cell therapy in solid tumors," Tina Albertson, M.D., Ph.D., Lyell’s chief medical officer, told BioSpace.