Clinical trial NCT06331169: Anlotinib With Trastuzumab Deruxtecan for Previously Treated HER2-Low Advanced Breast Cancer
Official title: A Prospective Phase Ib Study of Anlotinib With Trastuzumab Deruxtecan for HER2-Low Unresectable and/or Metastatic Breast Cancer (ALTER-BC-Ib-01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-03-26
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability and efficacy of anlotinib and trastuzumab deruxtecan in human epidermal growth factor receptor 2 (HER2)-low unresectable and/or metastatic breast cancer who had received ≤1 line of prior chemotherapy.


Eligibility criteria: Inclusion Criteria:

* 1. Age 18 - 75 years; ECOG PS 0 or 1. 2. Pathologically documented breast cancer that:

  1. Is unresectable or metastatic.
  2. Has a history of low HER2 expression (IHC 1+\& IHC 2+/ISH- or 0\<IHC\<1+).
  3. Is HR-positive or HR-negative.
  4. Has progressed on, and would no longer benefit from, endocrine therapy.
  5. Has been treated with ≥1 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting.

     3. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1（Previously treated lesions with radiotherapy or focal therapy and no progression cannot be included as target lesion for assessment）.

     4. Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions.

     5. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and after the last dose for at least 6 months.

     Exclusion Criteria:
     1. Has previously been treated with anti-angiogenic targeted small molecule therapy.
     2. Prior treatment with antibody drug conjugate with a topoisomerase I inhibitor exatecan derivative.
     3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
     4. Has unresolved toxicities from previous anticancer therapy.
     5. Has uncontrolled or significant cardiovascular disease.
     6. Has any bleeding event, unhealed wounds, ulcerative or fractures.
     7. Has arterial or venous thromboembolic events occurred within 6 months.
     8. Has spinal cord compression or clinically active central nervous system metastases.
     9. Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.

Primary outcomes:
measure: Determination of the RP2D of anlotinib in combination with trastuzumab deruxtecan
timeFrame: up to 1 year
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Duration of Response (DCR)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Jian Zhang
state: Shanghai
Study officials:
References: