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Ivonescimab plus chemotherapy has received breakthrough therapy designation as first-line therapy in patients with triple-negative breast cancer.
The National Medical Products Administration’s Center for Drug Evaluation (CDE) in China has granted breakthrough therapy designation (BTD) to ivonescimab in combination with chemotherapy for the frontline treatment of patients with triple-negative breast cancer (TNBC).1 This marks the fourth BTD awarded to ivonescimab by the CDE.
Ivonescimab also received BTD for use in combination with chemotherapy for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) resistant to EGFR TKI therapy; as frontline therapy for those with PD-L1–positive locally advanced or metastatic NSCLC; and in combination with docetaxel for those with locally advanced or metastatic NSCLC following prior PD-1/L1 inhibition and platinum-based chemotherapy. The former 2 designations have also since received approval for marketing in China.
The combination is being evaluated in the ongoing, phase 3 multicenter, randomized, double-blind HARMONi-BC1/AK112-308 trial (NCT06767527) in China.2 In February 2025, it was announced that the first patient had been enrolled onto this trial.3
Eligible patients include those between the ages of 18 and 75 years with histologically confirmed, unresectable locally advanced or metastatic, estrogen receptor, progesterone receptor, and HER2-negative breast cancer.2 Patients were required to be treatment naive, eligible for taxane monotherapy, have at least 1 measurable lesion per RECIST 1.1 criteria, adequate organ function, an ECOG performance status (PS) of 0 or 1, and life expectancy of at least 3 months.
In the trial, patients are randomly assigned to treatment with ivonescimab administered as an intravenous infusion plus 100 mg/m2 of IV nab-paclitaxel (Abraxane) on days 1, 8, and 15 of every 28-day cycle; or an IV placebo plus nab-paclitaxel.
The study’s primary end points are progression-free survival (PFS) according to an independent radiologic review committee (IRRC) and overall survival (OS). Secondary end points include safety, investigator-assessed PFS, and objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and time to response (TTR) all according to IRRC.
Previously reported findings from a phase 2 trial (NCT05227664), which were presented at the 2024 ESMO Congress, demonstrated that the regimen was active as first-line therapy in this population.4 The study enrolled patients with locally advanced unresectable or metastatic TNBC who had not received prior chemotherapy or targeted systemic therapy for their disease. Patients were required to have an ECOG PS of 0 or 1 and measurable disease per RECIST 1.1 criteria; at least 1 year was required between the last dose of prior neoadjuvant and adjuvant taxane therapy to disease recurrence.
All patients received 20 mg/kg of ivonescimab every 2 weeks plus either 90 mg/m2 of paclitaxel or 100 mg/m2 of nab-paclitaxel on days 1, 8, and 15 of every 28-day cycle. Patients were treated until disease progression or unacceptable toxicity.
The primary end points were ORR and adverse effects (AEs). Secondary end points were PFS, OS, DOR, and TTR.
Baseline characteristics of the population (n = 30) indicated that the median age was 54 years (range, 35-73). Most patients had an ECOG PS of 1 (53.3%), at least 4 (50.0%) or between 0 and 3 (46.7%) metastatic sites, and recurrent or metastatic disease (63.3%). Prior treatment for early-stage disease consisted predominantly of taxanes (60.0%), and most patients had PD-L1 combined positive scores (CPS) below 10 (80.0%).
Findings from the congress, which were presented with a median follow-up of 10.12 months, demonstrated that the ORR was 72.4% and the DCR was 100%. The median DOR was 7.49 months (95% CI, 3.91-not evaluable [NE]); the 6-month DOR rate was 68.9% (95% CI, 40.2%-85.9%). The median PFS was 9.30 months (95% CI, 6.24-NE); the 6-month PFS rate was 73.3% (95% CI, 51.8%-86.3%).
In the CPS below 10 population (n = 24), the ORR was 69.6% and the DCR was 100%. The median DOR was 7.49 months (95% CI, 3.91-NE), and the 6-month DOR rate was 68.4% (95% CI, 35.7%-87.0%). The median PFS was 9.3 months (95% CI, 5.55-NE), and the 6-month PFS rate was 71.2% (95% CI, 46.6%-86.0%).
Topline safety data showed that the most common treatment-related AEs (TRAEs) were decreased white blood cell count (any grade, 66.7%; grade 3/4, 16.7%), increased alanine aminotransferase levels (56.7%; 6.7%), alopecia (56.7%; 0%), and increased aspartate aminotransferase levels (56.7%; 6.7%).
No TRAEs led to permanent treatment discontinuation or death.
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