3 Key Takeaways
Plain English Summary- 01Core Finding
The primary endpoints were confirmed objective response rate and safety, assessed in the efficacy (real-world effectiveness in the trial)-evaluable population, defined as all patients who received one or more doses of study drug and had measurable disease at baseline and at least one efficacy assessment.
- 02Study Evidence
Tested in a early human trial (n=2) at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
What This Means for You
Treatment with first-line pumitamig plus nab-paclitaxel showed encouraging antitumour activity in patients with advanced or metastatic triple-negative breast cancer and a safety profile consistent with the mode of actions of both agents. These findings warrant further clinical evaluation in global Phase 2 and 3 trials.
The Discovery
Pumitamig, an investigational bispecific antibody targeting programmed death ligand-1 and vascular endothelial (blood-vessel lining) growth factor A, has shown preliminary efficacy (real-world effectiveness in the trial) across several tumour types. We aimed to evaluate the safety and activity of pumitamig plus nab-paclitaxel as first-line treatment in patients with advanced or metastatic triple-negative breast cancer.
In this single-arm, phase 1b/2 trial conducted at ten sites (hospitals and cancer centres) in China, patients aged 18-75 years with histologically documented, unresectable, locally advanced or metastatic triple-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 1 or less, and one or more measurable lesion (as per Response Evaluation Criteria in Solid Tumours, version 1.1) received first-line pumitamig (20 mg/kg intravenously once every 2 weeks) plus nab-paclitaxel (100 mg/m 2 intravenously on days 1, 8, and 15 of each 28-day cycle) until disease progression or unacceptable toxicity. In phase 1b, six patients received pumitamig (20 mg/kg once every 2 weeks intravenously plus nab-paclitaxel 100 mg/m 2 intravenously on days 1, 8, and 15 of each 28-day cycle) and were monitored for treatment-emergent adverse events, before subsequent enrolment in Phase 2. The primary endpoints were confirmed objective response rate and safety, assessed in the efficacy (real-world effectiveness in the trial)-evaluable population, defined as all patients who received one or more doses of study drug and had measurable disease at baseline and at least one efficacy assessment. This trial is registered with chictr.org.cn (ChiCTR2200060400) and ClinicalTrials.gov (NCT05918133), and is closed to recruitment.
Between June 27, 2022, and March 15, 2023, 42 patients were enrolled, received one or more doses of pumitamig plus nab-paclitaxel (median duration of exposure 9·0 months, 95% CI 6·9-11·7) and had one or more tumour assessments. All patients were Chinese and female; median age was 53 years (IQR 41-60). At a median follow-up of 35·2 months (95% CI 33·0-36·1), the confirmed objective response rate was 73·8% (95% CI 58·0-86·1; 31 of 42 patients), including one complete response and 30 partial responses. The most frequent treatment-related adverse events of grade 3 or worse were decreased neutrophil count (13 [a clinically meaningful level] of 42 patients), decreased white blood cell count (11 [26%]), proteinuria (six [14%]), and febrile neutropenia (five [12%]). Nine (21%) patients reported 14 treatment-related serious adverse events (alanine aminotransferase increased n=2; febrile neutropenia n=2; pancreatitis n=2; and ascites, aspartate aminotransferase increased, abdominal distension, γ-glutamyltransferase increased, blood alkaline phosphatase increased, cataract, macular oedema, and retinal vein occlusion all n=1). Treatment-related adverse events led to discontinuation of both nab-paclitaxel and pumitamig in four (10%) patients, discontinuation of nab-paclitaxel only in three (7%) patients, and discontinuation of pumitamig only in two (5%) patients. There were no treatment-related deaths.
How It Works, Simply
This oncology research focuses on antibodies. Researchers evaluated it using an early human trial (n=2) at the Phase I/II stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
The primary endpoints were confirmed objective response rate and safety, assessed in the efficacy-evaluable population, defined as all patients who received one or more doses of study drug and had measurable disease at baseline and at least one efficacy assessment.
- 02Study Evidence
Tested in a early human trial (n=2) at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Early human trial
Early human trial (n=2) · Phase I/II
Biological Pathway & Modality
Antibodies
Intervention: Activity and safety of first-line pumitamig plus nab-paclitaxel in triple-negative
Experimental Findings & Endpoints
Pumitamig, an investigational bispecific antibody targeting programmed death ligand-1 and vascular endothelial growth factor A, has shown preliminary efficacy across several tumour types.
We aimed to evaluate the safety and activity of pumitamig plus nab-paclitaxel as first-line treatment in patients with advanced or metastatic triple-negative breast cancer.
In this single-arm, phase 1b/2 trial conducted at ten sites (hospitals and cancer centres) in China, patients aged 18-75 years with histologically documented, unresectable, locally advanced or metastatic triple-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 1 or less, and one or more measurable lesion (as per Response Evaluation Criteria in Solid Tumours, version 1.1) received first-line pumitamig (20 mg/kg intravenously once every 2 weeks) plus nab-paclitaxel (100 mg/m 2 intravenously on days 1, 8, and 15 of each 28-day cycle) until disease progression or unacceptable toxicity. In phase 1b, six patients received pumitamig (20 mg/kg once every 2 weeks intravenously plus nab-paclitaxel 100 mg/m 2 intravenously on days 1, 8, and 15 of each 28-day cycle) and were monitored for treatment-emergent adverse events, before subsequent enrolment in Phase 2.
The primary endpoints were confirmed objective response rate and safety, assessed in the efficacy-evaluable population, defined as all patients who received one or more doses of study drug and had measurable disease at baseline and at least one efficacy assessment. This trial is registered with chictr.org.cn (ChiCTR2200060400) and ClinicalTrials.gov (NCT05918133), and is closed to recruitment.
Between June 27, 2022, and March 15, 2023, 42 patients were enrolled, received one or more doses of pumitamig plus nab-paclitaxel (median duration of exposure 9·0 months, 95% CI 6·9-11·7) and had one or more tumour assessments. All patients were Chinese and female; median age was 53 years (IQR 41-60).
At a median follow-up of 35·2 months (95% CI 33·0-36·1), the confirmed objective response rate was 73·8% (95% CI 58·0-86·1; 31 of 42 patients), including one complete response and 30 partial responses. The most frequent treatment-related adverse events of grade 3 or worse were decreased neutrophil count (13 [a clinically meaningful level] of 42 patients), decreased white blood cell count (11 [26%]), proteinuria (six [14%]), and febrile neutropenia (five [12%]).
Nine (21%) patients reported 14 treatment-related serious adverse events (alanine aminotransferase increased n=2; febrile neutropenia n=2; pancreatitis n=2; and ascites, aspartate aminotransferase increased, abdominal distension, γ-glutamyltransferase increased, blood alkaline phosphatase increased, cataract, macular oedema, and retinal vein occlusion all n=1). Treatment-related adverse events led to discontinuation of both nab-paclitaxel and pumitamig in four (10%) patients, discontinuation of nab-paclitaxel only in three (7%) patients, and discontinuation of pumitamig only in two (5%) patients.
There were no treatment-related deaths.
Clinical Translation & Practice Context
Treatment with first-line pumitamig plus nab-paclitaxel showed encouraging antitumour activity in patients with advanced or metastatic triple-negative breast cancer and a safety profile consistent with the mode of actions of both agents.
These findings warrant further clinical evaluation in global Phase 2 and 3 trials.
The Bottom Line · Clinical Pearl
“Treatment with first-line pumitamig plus nab-paclitaxel showed encouraging antitumour activity in patients with advanced or metastatic triple-negative breast cancer and a safety profile consistent with the mode of actions of both agents. These findings warrant further clinical evaluation in global Phase 2 and 3 trials.”
Published in The Lancet Oncology · Current Stage: Phase I/II