The CARMEN-LC03 trial analyzing tusamitamab ravtansine (tusa rav) versus docetaxel in patients with previously treated non-squamous non-small cell lung cancer (NSCLC) ended early after failing to show improvement in progression-free survival (PFS) or overall survival (OS). However, it did show a positive trend for health-related quality of life (HRQoL) and appeared to be better tolerated by patients than docetaxel.
“CARMEN-LC03 did not meet its primary objective of PFS and OS,” said Benjamin Besse, MD, Professor and Director of Clinical Research at Gustave Roussy Cancer Campus, Villejuif, France. “There was a positive trend for OS, and subgroup analysis suggests a trend of improved PFS for tusa rav among patients with high CEACAM5 expression. And tusa rav demonstrated a safety profile that is favorable compared to docetaxel. CARMEN-LC03 was discontinued in December 2023, but patients benefiting from treatment could continue to receive tusa rav.”
Prof. Besse reported the final PFS data and the first planned interim OS analysis during a session titled The New Generation of Cytotoxics at the 2024 World Conference on Lung Cancer.
Tusa rav is an antibody-drug conjugate that targets transmembrane glycoprotein CEACAM5 with DM4, an antimitotic agent that can inhibit cell proliferation.
“Patients with non-squamous NSCLC who progress on immunotherapy and chemotherapy usually receive docetaxel-containing regimens with suboptimal outcomes,” Prof. Besse said. “CEACAM5 is overexpressed in non-squamous NSCLC in up to 25% of patients.”
The CARMEN-LC03 trial randomized patients with non-squamous NSCLC who were previously treated with platinum-based chemotherapy and immune checkpoint inhibition whose CEACAM5 expressions involved at least 50% of tumor cells to either tusa rav (194 patients) or docetaxel (194 patients).
The study design called for a total of 450 patients, 225 in each arm, he said, with 389 patients randomized when the trial was halted. Nineteen percent of patients in the tusa rav arm remained in treatment at termination as did 13% of patients in the docetaxel arm.
Secondary endpoints included overall response rate (ORR), safety, HRQoL, and duration of response (DoR).
Final PFS was 5 months for tusa rav compared to 6 months for docetaxel, HR 1.14 (95% CI 0.86-1.51, p = 0.8204). A planned interim analysis showed OS of 13 months for tusa rav versus 12 months for docetaxel, HR 0.85 (95% CI 0.64-1.11, p = 0.112). Patients with more than 80% CEACAM5 expression had improved PFS and OS on tusa rav compared to docetaxel.
The median patient age was 64, the majority (60%) were men, and most had previously received one or two prior lines of therapy.
Time to deterioration of HRQoL favored tusa rav, with 3 months with tusa rav versus 2 months for docetaxel, Prof. Besse said. Scores for physical functioning and role functioning were also better for tusa rav compared to docetaxel at 8 months versus 4 months and 6 months versus 4 months, respectively.
Both arms had similar rates of treatment-emergent adverse events (TEAEs), around 95%, but grade 3 and higher TEAEs were lower for tusa rav at 41% versus 58% for docetaxel.
Treatment-related adverse events (TRAEs) were lower in the tusa rav arm at 73% versus 86% for docetaxel, as were grade 3 and higher TRAEs at 15% and 40%, respectively.
TEAEs leading to dose reduction and treatment discontinuation for tusa rav were roughly half the rates for docetaxel at 17% versus 36% and 8% versus 17%, respectively. However, TEAs leading to dose delay were higher for tusa rav at 43% versus 28%, which was largely due to corneal events.
One-quarter of tusa rav patients had corneal events at 15% keratopathy and 11% keratitis versus 0.6% for both in the docetaxel arm. Neutropenia was the most common adverse event in the docetaxel arm at 73% with 57% being greater than or equal to grade 3.
