Untreated advanced non–small cell lung cancer (NSCLC). Adult patients with stage IIIB, IIIC, or IV disease without actionable genomic alterations can join a randomized, open-label, phase 3 study testing the survival advantage of datopotamab deruxtecan (Dato-DXd) (AstraZeneca/Daiichi Sankyo). Dato-DXd is one of a half dozen experimental antibody-drug conjugates that target TROP2, a transmembrane glycoprotein that is overexpressed in several solid tumors, including NSCLC. One group of participants will receive an intravenous (IV) infusion of Dato-DXd plus durvalumab (Imfinzi) for up to 4 years, and over the first 12 weeks, they will receive four rounds of IV carboplatin (Paraplatin). The other group will receive IV infusions of pembrolizumab (Keytruda) every 3 weeks plus a combination of standard IV chemotherapy appropriate for the patient’s histology (nonsquamous or squamous NSCLC). In the United States, centers in Arkansas, Nebraska, Ohio, and Texas started recruiting in December 2020; trial sites are planned in 16 other states and 23 other countries. The trialists plan to enroll 1,000 participants. Overall survival (OS) and progression-free survival (PFS) are the primary endpoints; quality of life (QoL) is not being tracked. More details at clinicaltrials.gov.
Untreated advanced or metastatic NSCLC. Adult patients in this clinical situation without actionable genomic alterations as well as those with a PD-L1 tumor proportion score (TPS) of < 50% are eligible to participate in a randomized, open-label, phase 3 trial of Dato-DXd in combination with pembrolizumab, with or without chemotherapy. One group of participants will receive IV Dato-DXd and pembrolizumab every 3 weeks. For the second group of patients, IV platinum chemotherapy will be added to the Dato-DXd and pembrolizumab for the first four rounds of treatment. The third group of individuals make up the comparator arm and will receive thrice-weekly IV pembrolizumab, pemetrexed (Alimta), plus platinum chemotherapy. All participants will be treated for approximately 2.5 years or until disease progression or death. The trial began recruiting 975 participants in Arizona, Florida, Maryland, and New Jersey, and in Japan in January 2023. The primary endpoints are OS and PFS; QoL will not be assessed. More details at clinicaltrials.gov.
Metastatic NSCLC. Individuals with this cancer who have a TPS of > 50% can also receive an antibody-drug conjugate targeting TROP2 in combination with pembrolizumab. This time, the product is sacituzumab govitecan (Trodelvy). The randomized, open-label phase 3 trial is testing whether the two drugs in combination improve survival and slow progression better than pembrolizumab alone. For approximately 2 years, one group of people in the trial will receive IV pembrolizumab every 3 weeks. The other group, in addition to the pembrolizumab, will receive IV sacituzumab govitecan weekly for 2 weeks then 1 week off until unacceptable toxicity, disease progression, withdrawal of consent, or death. Study sites in the states of Florida and Georgia, and in Australia, Taiwan, and Turkey, opened in February 2023 with the aim of recruiting 614 participants. Overall survival over 4 years and PFS are the primary outcomes. QoL is a secondary outcome. More details at clinicaltrials.gov.
Unresectable metastatic NSCLC. Individuals with this type of lung cancer are being recruited for a nonrandomized, phase 1/2 study to determine whether a combination of amivantamab (Rybrevant) and capmatinib (Tabrecta) is tolerable and more effective than either therapy alone. The two drugs inhibit different stages of mesenchymal-epithelial transition (MET), a step in cell development that is crucial for metastasis because it enhances cell mobility, invasion, and resistance to apoptosis. In the phase 1 study, participants will start with twice-daily tablets of capmatinib and IV amivantamab once weekly for 4 weeks then every 2 weeks. Doses will be adjusted on the basis of toxicities. In phase 2, a new group of participants will receive the refined doses for up to 2 years until progression or death. The study opened at the Oncology Institute of Hope and Innovation in Whittier, Calif., in December 2020 with the aim of recruiting 161 participants. Sites are gearing up in five more U.S. states and in Canada, Europe, and Asia. Objective response rate is the primary outcome of the phase 2 study, with OS and QoL as secondary endpoints. More details at clinicaltrials.gov.
Locally advanced or metastatic NSCLC with EGFR-exon-20 insertion mutations. Adults with this diagnosis who have not yet been treated and are not amenable to curative surgery or radiotherapy are sought for a randomized, open-label phase 3 trial testing whether investigational EGFR tyrosine-kinase inhibitor furmonertinib (from ArriVent) is more effective than chemotherapy for first-line treatment. Chemotherapy is currently standard of care in this indication with targeted therapies amivantamab-vmjw (Rybrevant) and mobocertinib succinate (Exkivity) as second-line options. Individuals in the trial will take daily tablets of furmonertinib or platinum-based IV chemotherapy for 32 months or until disease progression, whichever comes first. The study opened in December in sites across 15 U.S. states. Centers in a further nine states are gearing up, with the aim of enrolling a total of 375 people. The primary outcome is PFS. QoL and OS at 5 years are secondary outcomes. More details at clinicaltrials.gov.
NSCLC previously treated with at least one platinum chemotherapy and at least one targeted treatment. Adults aged 70 or younger with this type of lung cancer are eligible for a National Cancer Institute phase 2 investigation of autologous T-cell receptor (TCR) gene therapy. Unlike CAR T-cell therapy, which only reaches the 20% of cancer neoantigens that are expressed extracellularly, TCR technology can target the 80% of abnormal proteins that are expressed inside cancer cells. Participants will receive a single infusion of their own engineered T cells. They will attend follow-up visits every 3-6 months for 3 years, then join a long-term study in which they will be followed for 12 more years. The National Institutes of Health Clinical Center in Bethesda, Md., started recruiting for the trial’s 210 participants with one of a selection of solid cancers in February 2023. Response rate measured by objective tumor regression is the primary endpoint. OS and QoL will not be tracked. More details at clinicaltrials.gov.
All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).
A version of this article first appeared on Medscape.com.
Editor’s note: This article was changed on 24 February to remove an incorrect reference to osimertinib.
