A Study of QL1706 Combined With Short-Cycle Anthracyclines or Taxanes for the Treatment of Early-Stage TNBC

Summary

Triple-negative breast cancer (TNBC) accounts for about 20% of breast cancers, is poorly differentiated, progresses rapidly, and frequently recurs, making it the subtype with the worst prognosis. Owing to the absence of actionable receptors on tumor cells, chemotherapy has historically been the mainstay of TNBC treatment.

With advances in basic research, more immune checkpoint inhibitors (ICIs) targeting distinct pathways have entered clinical use. Avellutolimab (QL1706) combines two engineered monoclonal antibodies-anti-PD-1 and anti-CTLA-4-in a fixed \~2:1 ratio. By blocking PD-1, it inhibits immune escape; by blocking CTLA-4, it relieves immune suppression and activates antitumor immunity. Preclinical studies show QL1706 has stronger antitumor activity than either anti-PD-1 or anti-CTLA-4 alone. Clinically, QL1706 monotherapy demonstrated notable efficacy as second-line therapy for advanced cervical cancer, with a median PFS of 5.4 months and manageable safety (2% discontinuation due to adverse events). Based on these data, QL1706 was approved in September 2024 for patients with recurrent or metastatic cervical cancer progressing after prior platinum-based therapy.

In the TNBC immunotherapy era, the optimal chemotherapy backbone remains uncertain, raising two key questions. First, with the introduction of immunotherapy-especially dual ICI regimens-can chemotherapy be de-escalated, and which patients are suitable for such de-escalation? Second, should anthracyclines be retained within immunotherapy-based regimens? The single-arm cTRIO study (ASCO 2023) used six cycles of paclitaxel plus carboplatin plus anti-PD-1 and achieved a pCR rate of 56.5%, despite enrolling patients with more advanced disease and higher nodal positivity. In contrast, translational analyses from NeoTENNIS (2024) suggest anthracyclines may promote immune activation and enhance the effects of immunotherapy. Consequently, small-sample exploratory clinical studies are needed to assess the feasibility of anthracycline-sparing chemotherapy strategies in the TNBC immunotherapy era.

For these reasons, we propose an exploratory neoadjuvant study in patients with early-stage TNBC using four cycles of QL1706 combined with either a taxane or an anthracycline. The study plans to enroll 30 patients with early-stage TNBC. Eligible patients will be randomized using a random number table into two cohorts for exploration: Cohort 1) QL1706 combined with nab-paclitaxel and carboplatin; Cohort 2) QL1706 combined with pirarubicin and cyclophosphamide. If a pCR is achieved, no further chemotherapy will be administered. If a pCR is not achieved, patients will subsequently receive four additional cycles of QL1706 plus pirarubicin and cyclophosphamide and four additional cycles of QL1706 plus nab-paclitaxel and carboplatin, respectively.

Conditions

• TNBC, Triple Negative Breast Cancer

Interventions

DRUG

Cyclophosphamide

cyclophosphamide

DRUG

QL1706 (bispecific antibody targeting PD-1 and CLTA-4)

QL1706

DRUG

Pirarubicin

pirarubicin

DRUG

Nab-paclitaxel

nab-paclitaxel

DRUG

Carboplatin (AUC 5)

carboplatin

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.

  collaborator INDUSTRY

• Xijing Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-11-06

Primary Completion

2027-08-01

Completion

2030-08-01

Countries

• China

Study Locations