A clinical trial to study the safety and tolerability of Trastuzumab Deruxtecan drug alone, and in combination with other drugs like durvalumab, pertuzumab and paclitaxel in patients with breast cancer

Phase 1

• Conditions: Health Condition 1: C509- Malignant neoplasm of breast of unspecified site

• Registration Number: CTRI/2021/03/031928
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

Informed consent

1.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

2. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the AstraZeneca Genomic Initiative

Age

3. Patient must be = 18 years of age at the time of signing the informed consent

Type of patient and disease characteristics

4. Male or female patients who have pathologically documented breast cancer that:

(a) Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic.

(b) Is HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment according to ASCO/CAP guidelines

(c) Is documented as hormone receptor-positive (either oestrogen receptor and/or progesterone receptor positive [oestrogen receptor or progesterone receptor = 1%]) or negative as per ASCO/CAP guidelines in the metastatic setting.

5. Patients must provide an adequate tissue sample: either FFPE tissue blocks (preferred) or at least 20 freshly-cut unstained serial tumour slides.

6. ECOG PS of 0 or 1

7. Part 1 of each module:

(a) Radiological or objective evidence of disease progression on or after the last systemic therapy prior to starting study treatment.

(b) At least 1 prior treatment line in metastatic setting required. A ‘treatment line’ may consist of endocrine therapy, chemotherapy and/or anti-HER2 therapy, or a combination of any of these. Prior taxane, trastuzumab and pertuzumab exposure is allowed.

8. Part 2 of each module:

(a) No prior lines of therapy for advanced/MBC allowed. (Additional requirement: at least 12 months since last adjuvant HER2-targeted therapy, or chemotherapy required). Prior taxane, trastuzumab and pertuzumab exposure is allowed in the adjuvant or neoadjuvant setting.

9. LVEF = 50% within 28 days before enrolment.

10. Adequate organ and bone marrow function within 14 days before treatment assignment

11. Minimum life expectancy of 12 weeks at screening.

12. At least one lesion, not previously irradiated, that qualifies as a RECIST 1.1 TL at baseline.

13. Has adequate treatment washout period before randomisation/enrolment,

Reproduction

14. Evidence of post-menopausal status or negative serum pregnancy test for females of child-bearing potential who are sexually active with a non-sterilised male partner.

15. Female patients of child-bearing potential who are sexually active with a non-sterilised male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 7 months after the last dose of study treatment.

16. Non-sterilised male patients who are sexually active with a female partner of child-bearing potential must use a condom with spermicide from screening to 4 months after the final dose of study treatment

Exclusion Criteria

Medical Conditions

1Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

2Uncontrolled or significant cardiovascular disease

3Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

4Lung criteria:

(a)Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)

(b)Any autoimmune, connective tissue or inflammatory disorders (eg, Rheumatoid arthritis, Sjogren’s, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.

(c)Prior pneumonectomy.

5Active primary immunodeficiency, known human HIV infection, or active hepatitis B or C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects should be tested for HIV prior to enrolment if required by local regulations or IRB/EC.

6History of another primary malignancy except for:

(a)Malignancy treated with curative intent and with no known active disease = 5 years before the first dose of study treatment

(b)Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

(c)Adequately treated carcinoma in situ without evidence of disease

7Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, Wegener syndrome [granulomatosis with polyangiitis], Graves’ disease, and rheumatoid arthritis, hypophysitis, uveitis, etc).

8Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

9Patients with spinal cord compression or a history of leptomeningeal carcinomatosis.

10Has untreated CNS metastases identified either on the baseline brain imaging obtained during the screening period or identified prior to signing the ICF.

Prior/Concomitant Therapy

11Patients who have received prior immune checkpoint inhibitors.

12Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment.

13Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade = 1 or baseline.

14Any concurrent chemotherapy, study treatment, or biologic for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.

15Prior treatment with an ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor

Prior/Concurrent Clinica

Study & Design

• Study Type: Interventional
• Study Design: Not specified