Neoadjuvant Inetetamab Combo Shows Efficacy, Tolerability in Locally Advanced HER2+ Breast Cancer

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The combination of inetetamab (cipterbin), pertuzumab (Perjeta), paclitaxel, and carboplatin (TCbIP) administered elicited responses with an acceptable safety profile when administered as neoadjuvant treatment in patients with locally advanced HER2-positive breast cancer, according to data from the primary analysis of a phase 2 study (NCT05749016) presented at the 2023 ESMO Congress.¹

In the intention-to-treat (ITT) population (n = 23), the objective response rate (ORR) achieved with the combination was 91.3%, which included a complete response (CR) rate of 47.8%, a partial response (PR) rate of 43.5, and a stable disease (SD) rate of 8.7%. In the per-protocol (PP) population (n = 16), the ORR was 93.8%, which included a CR rate of 62.5%, a PR rate of 31.3%, and a SD rate of 6.2%. The pathologic complete response (pCR) rate was 62.5% and the near pCR (nPCR) rate was 87.5%.

“Neoadjuvant therapy with TCbIP has shown promising efficacy and manageable toxicity in patients with HER2-positive locally advanced breast cancer,” Yue Chai, MD, of the Medical Oncology Department in the Chinese Academy of Medical Sciences and Peking Union Medical College – National Cancer Center, Cancer Hospital in Beijing, China, and colleagues, said in a presentation of the data.

The neotype HER2-targeted monoclonal antibody inetetamab has an amino acid–modified Fc segment that enhances the antibody-dependent cellular cytotoxic effect.

Because data are lacking with regard to the safety and efficacy of TCbIP in the neoadjuvant setting for this population, investigators launched the single-arm, open-label, phase 2 study, which enrolled patients with histologically confirmed HER2-positive primary invasive, stage IIA to IIIC breast cancer. Patients needed to be between 18 years and 70 years, have an ECOG performance status of 0 to 1, and left ventricular ejection fraction (LVEF) of at least 50%. Patients could not have a history of systemic treatment for their disease.

Study participants received TCbIP every 3 weeks for up to 6 cycles followed by surgery. Treatment continued until progressive disease or unacceptable toxicity.

pCR served at the trial’s primary end point, and key secondary end points comprised nPCR, ORR, and safety.

A total of 28 patients were enrolled between November 2021 and May 2023. Sixteen of these patients received 6 cycles of study treatment and underwent surgery, 1 received 2 cycles of treatment and then withdrew due to personal reasons, 6 received 2 cycles of treatment and were still receiving treatment, 1 had 1 cycle of treatment and was lost to follow-up without surgery, and 4 received 1 cycle of treatment and were still receiving treatment.

Twenty-three of these patients comprised the ITT population and 16 comprised the PP population. All 28 patients were included in the safety population.

In the total population, the median age was 53 years (range, 30-64); 10.7% of patients had a median age of 35 years or younger, 32.1% had a median age ranging from 36 years to 49 years, and 57.1% had a median age of 50 years or older. More than half of patients were postmenopausal (57.1%). Regarding T stage, 64.3% were stage 2, 17.9% were stage 3, 14.3% were stage 4, and 3.6% were stage 1. In terms of N stage, 50.0% were stage 2, 25.0% were stage 3, 21.4% were stage 1, and 3.6% were stage 0.

Moreover, 53.6% of patients were estrogen receptor (ER) and progesterone receptor negative; 46.4% were ER and/or progesterone positive. Three-quarters of patients were HER2 immunohistochemistry (IHC) 3+ status and the remainder were IHC 2+ and FISH positive. Additionally, 42.9% and 57.1% of patients had a Ki-67 level of up to 30% or over 30%, respectively. Regarding histologic grade, 64.2% had grade 2 disease, 10.7% had grade 3 disease, and this was unknown for 25.0% of patients.

Regarding safety, the most common non-hematological adverse effects (AEs) included nausea or vomiting (grade 1/2, 42.9%; grade 3/4, 3.6%), fatigue (50.0%; 0%), diarrhea (28.6%; 0%), abdominal pain (3.6%; 0%), alopecia (53.6%; 0%), peripheral sensory (7.1%; 0%), mucositis (10.7%; 0%), increased aspartate or alanine aminotransferase (17.9%; 0%), and elevated creatinine (7.1%; 0%).

The most common hematological AEs comprised leucopenia (17.9%; 3.6%), neutropenia (14.3%; 25.0%), febrile neutropenia (0%; 3.6%), thrombocytopenia (21.4%; 3.6%), and anemia (39.3%; 0%).

No significant reduction in the LVEF was observed in any patient, the study authors concluded.

Editor’s Note: Dr Chai and authors did not declare any conflicts of interest.

Reference

Chai Y, Jiang M, Liu J, et al. Neoadjuvant inetetamab combined with pertuzumab, paclitaxel and carboplatin for locally advanced HER2-positive breast cancer: primary analysis of a phase II study. Ann Oncol. 2023;34(suppl 2):S327. doi:10.1016/j.annonc.2023.09.539