The safety of datopotamab deruxtecan-dlnk (Datroway) was evaluated in 360 individuals with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who received at least one dose of deruxtecan-dlnk (Datroway) 6 mg/kg in the TROPION-Breast01 trial. Deruxtecan-dlnk (Datroway) was administered by intravenous infusion once every 3 weeks. The median duration of treatment was 6.7 months (range, 0.7–16.1 months) for individuals who received deruxtecan-dlnk (Datroway). Serious adverse reactions occurred in 15% of individuals who received deruxtecan-dlnk (Datroway). Serious adverse reactions in more than 0.5% of individuals who received deruxtecan-dlnk (Datroway) were urinary tract infection (1.9%), COVID-19 infection (1.7%), interstitial lung disease (ILD)/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of individuals who received deruxtecan-dlnk (Datroway) and were due to ILD/pneumonitis. The study demonstrated a statistically significant improvement in progression-free survival (PFS) in individuals
randomly assigned to deruxtecan-dlnk (Datroway) compared to chemotherapy.
The efficacy of datopotamab deruxtecan-dlnk (Datroway) was evaluated in a pooled subgroup of individuals with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who were enrolled across two clinical studies: TROPION-Lung05 and TROPION-Lung01. TROPION-Lung05 (NCT04484142) was a global, multicenter, single-arm, open-label trial in individuals with previously treated NSCLC with an actionable genomic alteration; TROPION-Lung01 (NCT04656652) was a global, multicenter, randomized, active-controlled, open-label trial in individuals with previously treated NSCLC with or without an actionable genomic alteration. For both trials, eligible individuals with EGFR-mutated NSCLC must have previously received an EGFR-directed therapy and platinum-based chemotherapy. Individuals with a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening were ineligible. Individuals who had brain metastases that were untreated and symptomatic were also ineligible. Individuals received deruxtecan-dlnk (Datroway) 6 mg/kg by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression.
For the pooled efficacy population, the major efficacy outcome measure was overall response rate (ORR). An additional efficacy outcome was duration of response (DOR). Efficacy was assessed in 114 individuals with EGFR-mutated NSCLC. Fifty-three percent (53%) of individuals had tumors with exon 19 deletions, 34% had exon 21 L858R mutations, 28% had T790M mutations, 2.6% had exon 20 insertion mutations, and 14% had other EGFR mutations. Four percent (4.4%) of individuals received one prior line of systemic therapy, 39% received two prior lines of systemic therapy, and 57% received three or more prior lines of systemic therapy in the locally advanced or metastatic setting. The confirmed ORR was 35.8% (95% CI, 27.8–44.4) overall, and 43.6% (95% CI, 32.4–55.3) and 23.5% (95% CI, 10.7–41.2) in those with EGFR mutations and ALK rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2–9.8), and the overall disease control rate was 78.8% (95% CI, 71.0–85.3). The most common treatment-related adverse event was stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) individuals experienced adjudicated treatment-related ILD/pneumonitis, with one (0.7%) grade 5 event.
OFF-LABEL INDICATION
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
