Memorial Sloan Kettering Cancer Center (MSK) researchers presented breakthrough advances in new treatment approaches for several cancer types at the 2024 ASCO Annual Meeting held May 31 to June 4, 2023, in Chicago. Highlights of practice-changing study results in HPV-associated neck cancer, tenosynovial giant cell tumor, renal cell carcinoma, lung cancer, and more were as follows:
Head and Neck Cancer: Hypoxia-Directed Lower Dose Radiation for HPV-Associated Cancer — Without Surgery
Tumor hypoxia reduces the effectiveness of chemoradiotherapy and is associated with poor outcomes. MSK researchers have been testing whether a lower-dose radiation strategy can be given to patients whose tumors are non-hypoxic to determine whether it’s possible to reduce toxicities without compromising oncologic outcomes.
MSK researchers previously reported that hypoxia-directed de-escalated neck radiation followed by primary tumor surgery with intact nodal disease produced excellent outcomes with dramatically reduced long-term side effects for patients with human papillomavirus (HPV)-associated oropharyngeal cancer. The results from the trial (NCT03323463) were published in the Journal of Clinical Oncology in January 2024.
At ASCO 2024, principal investigator radiation oncologist Nancy Lee, MD, FASTRO, Vice Chair of the Department of Radiation Oncology, Service Chief of Head and Neck Radiation Oncology, and Service Chief of Proton Therapy at MSK, presented results from the successor trial testing hypoxia-directed de-escalated chemoradiotherapy with no surgery. The early data continue to show that this treatment strategy significantly reduced treatment toxicity without compromising survival.
A total of 111 HPV-positive oropharyngeal cancer patients without evidence of tumor hypoxia on 18 F-fluoromisonidazole positron emission tomography imaging received de-escalated chemoradiation to 30 Gray (Gy). Thirty-nine patients with persistent evidence of hypoxia received 70 Gy.
At two years of median follow-up, local failure, regional failure, and distant metastasis rates for the lower dose cohort were 4.2%, 6.9%, and 2.0%, respectively, and the two-year overall survival (OS) probability was 99%. Acute grades 3 and 4 toxicities occurred in 32% of patients, with 67% of events due to neutropenia. Mean patient-reported dysphagia outcome scores were 93 at baseline, 68 at three weeks, and 91 at four months after chemoradiation with the lower dose strategy.
The MSK research team included experts from the Departments of Radiation Oncology, Medical Oncology, Radiology, Surgery, Medical Physics, and Pathology. An FDA-approved phase 3 multicenter trial comparing this personalized treatment strategy to the standard one-size-fits-all approach of every patient receiving 70 Gy will be initiated this summer.
Beyond the present study, Dr. Lee and colleagues are also investigating a lower-dose radiation strategy for patients with HPV-associated cancers not eligible for the 30 Gy approach due to size or other characteristics. Learn more.
Read ASCO 2024 Abstract 6007. The study was supported by funding from the National Cancer Institute, the DIMON HPV Foundation, the Serra Initiative on the Management of Head and Neck Cancer Side Effects, and the James A. Rowen Precision Radiotherapy Fund. Access disclosures for Dr. Lee.
Tenosynovial Giant Cell Cancer: Targeted Therapy Achieves Robust Response and Significant Improvements in Outcomes
The targeted therapy vimseltinib, a selective inhibitor of the tyrosine kinase receptor colony- stimulating factor 1 receptor (CSF1R), demonstrated a robust objective response rate (ORR) and resulted in significant and clinically meaningful functional and symptomatic improvements in patients with tenosynovial giant cell tumor (TGCT), according to results from the global phase 3 MOTION trial (NCT05059262).
William Tap, MD, Chief of the Sarcoma Medical Oncology Service at MSK and senior author of the study, presented the trial’s primary results. The paper was published simultaneously in The Lancet.
Results for ORR, the primary endpoint, and all secondary endpoints were statistically significant. A total of 123 patients were randomized 2:1 to receive oral vimseltinib (83 patients) or a placebo (40 patients). The ORR was significantly higher for vimseltinib at 40% versus 0% for the placebo.
Most treatment-emergent adverse events were grade 1 or 2, and the only grade 3 or 4 event in more than 5% of patients was increased blood creatinine phosphokinase, which was not thought to be clinically significant. There was no evidence of liver toxicity with vimseltinib.
These very positive results demonstrate that vimseltinib has the potential to become the standard of care systemic therapy for TGCT. If so, it will be a welcome advance since current treatment options for patients with inoperable TGCT are limited and associated with a rare and unpredictable risk of serious liver toxicity.
Read ASCO 2024 Abstract 11500. The study was funded by Deciphera Pharmaceuticals, LLC. Access disclosures for Dr. Tap.
Kidney Cancer: Long-Term Efficacy Benefits for Immune Checkpoint Inhibitor and Targeted Therapy Combination
The anti-PD-L1 inhibitor avelumab plus the highly-selective vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib as a first-line therapy showed significantly prolonged progression-free survival (PFS) in patients with PD-L1-positive advanced renal cell carcinoma versus sunitinib at a median follow-up of at least six months, according to initial results of the global JAVELIN Renal 101 phase 3 trial (NCT02684006). The primary study results were published previously in The New England Journal of Medicine.
At ASCO 2024, lead author Robert Motzer, MD, Section Head, Kidney Cancer, Genitourinary Oncology Service and the Jack and Dorothy Byrne Chair in Clinical Oncology at MSK presented final OS results after at least 68 months, the longest reported follow-up to date for a phase 3 trial of an immune checkpoint inhibitor plus tyrosine kinase inhibitor combination in advanced renal cell carcinoma.
Interestingly, while median OS favored avelumab plus axitinib versus sunitinib for favorable-, intermediate-, and poor-risk groups, the differences were not statistically significant. However, avelumab plus axitinib showed longer-term efficacy benefits versus sunitinib alone, including prolonged PFS (13.9 months versus 8.5 months), a nearly doubled ORR (59.7% versus 32%), and a longer duration of response (19.4 months versus 14.5 months), respectively. Long-term safety was manageable and in line with previous analyses.
The long-term results from this clinical trial demonstrate that avelumab plus axitinib provided long-term efficacy benefits and a manageable safety profile in patients with advanced kidney cancer. However, there was not a significant benefit in overall survival for the combination compared to sunitinib at this final analysis.
Read ASCO 2024 Abstract 4508. The study was sponsored by Pfizer and conducted under an alliance between Pfizer and Merck KGaA (Darmstadt, Germany). Access disclosures for Dr. Motzer.
Other Notable MSK Research News from ASCO 2024:
Lung Cancer with Active Central Nervous System Disease: Targeted Therapy Combination Shows Promising Activity
Amivantamab plus lazertinib achieved clinically meaningful radiographic response and time on treatment in patients with epidermal growth factor receptor (EGFR)-mutant lung cancer and progressive central nervous system metastases in an MSK-exclusive phase 2 trial (NCT04965090). The study was the first clinical trial successfully completed in this patient population with active brain metastases or leptomeningeal disease.
Amivantamab is a bispecific monoclonal antibody, and lazertinib is an oral, third-generation, brain-penetrant EGFR tyrosine kinase inhibitor. The trial enrolled 20 patients with progressive or new brain metastases and 22 with leptomeningeal disease. All patients with EGFR exon 19 deletions/L858R/atypical mutations received prior treatment with osimertinib, and all patients with EGFR exon 20 insertions had prior chemotherapy.
For the brain metastases cohort, the systemic response rate was 30% and the intracranial response rate was 40%. In the leptomeningeal disease cohort, the systemic response was 33% and the median time on treatment was 8.3 months. The median progression free survival was 5.9 months for the brain metastases cohort and 8.3 months for the leptomeningeal disease cohort. Overall survival was 17.9 and 14.4 months, respectively.
The investigators will present genomic data comparing concurrent systemic tumor, plasma, and cerebrospinal fluid samples, as well as circulating tumor DNA and circulating free RNA data in the future.
Read ASCO Abstract 8517, presented by lead author MSK thoracic oncologist and early drug development specialist Helena Yu, MD. The trial was sponsored by MSK in collaboration with Janssen Scientific Affairs. Access disclosures for Dr. Yu.
Non-Small Cell Lung Cancer: Extended Follow-up Data from the CodeBreaK 101 International Trial
Rational combination regimens are urgently needed to improve efficacy for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) in the first-line setting. Sotorasib, a first-in-class KRAS G12C inhibitor, plus platinum doublet chemotherapy showed promising early results in patients with chemotherapy-refractory disease in the global phase 1b CodeBreaK 101 trial (NCT04185883), as previously presented at the World Conference on Lung Cancer in 2023.
At ASCO 2024, lead author thoracic oncologist and early drug development specialist Bob Li, MD, PhD, MPH presented extended follow-up data from this international phase 1 trial for patients with KRAS G12C-mutated NSCLC treated in the first-line treatment setting and beyond.
Sotorasib plus pemetrexed and carboplatin showed robust, durable responses with a manageable safety profile in patients treated in all treatment settings. For patients treated in the first-line setting, the ORR was 65%, the disease control rate was 100%, and the median PFS was 10.8 months. For patients with PD-L1 expression less than 1%, the median PFS was 11.9 months. OS data remain immature and will be reported in a future update.
These results support continuing evaluation of sorotasib plus pemetrexed and carboplatin in the ongoing international CodeBreaK 202 phase 3 registrational trial in treatment-naïve, PD-L1-negative, KRAS G12C-mutated NSCLC as a potential new first-line treatment for these patients (NCT05920356).
Read ASCO Abstract 8512. The study was sponsored by Amgen. Access disclosures for Dr. Li.
Solid Tumors: Encouraging Phase 1 Results for Bispecific Antibody As Monotherapy or in Combination with Pembrolizumab
The bispecific antibody MCLA-145 given alone or in combination with pembrolizumab was well-tolerated and demonstrated a manageable safety profile with encouraging clinical responses, including in patients who relapsed after anti-PD-L1 therapies, according to data from an ongoing global phase 1 trial (NCT03922204).
MCLA-145 targets CD137 and the PD-1/PD-L1 axis, aiming to enhance antigen-mediated T cell activation and block inhibitory PD-L1. As of December 2023, 72 patients with 26 cancer types received treatment, including 25% with NSCLC.
MCLA-145 alone or in combination was well tolerated and had a manageable safety profile. The recommended dose for expansion was established at 40 mg. Analysis of peripheral blood Ki67+ CD8 T cells supported maximal pharmacodynamics at 40 mg.
Overall, the preliminary disease control rate was 37% with monotherapy and 68% with the combination. In the monotherapy group, there were five partial responses in patients with glioblastoma, sarcoma, and cervical, anal, and gastric cancer. In the combination therapy group, there was one partial response in Merkel cell carcinoma and one complete response in PD-L1-positive NSCLC.
Read ASCO Abstract 2520 presented by gynecologic oncologist and early drug development specialist Chrisann Kyi, MD, principal investigator of the trial at MSK. The study was sponsored by Merus N.V. Access disclosures for Dr. Kyi.