Study of neoadjuvant patritumab deruxtecan with or without endocrine therapy in previously untreated patients – VALENTINE trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Solti Group

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Nov 2022 → ongoing

Decision date (initial)

2024-01-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo

External identifiers

EU CT number

2023-503403-28-00

EudraCT number

2022-001181-36

ClinicalTrials.gov

NCT05569811

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To evaluate the efficacy of HER3-DXd at 5.6 mg/kg (either alone or in combination with letrozole) given to subjects with operable early breast cancer as a neoadjuvant treatment scheduled.

Secondary objectives 7

1. Evaluate other parameters of the efficacy of HER3-DXd (alone or in combination with letrozole) and Chemotherapy (CT)
2. Evaluate long term efficacy outcomes of HER3-DXd (alone or in combination with letrozole) and CT.
3. Evaluate CelTIL score at C1D21, and its ability to predict pathological response at surgery and other response endpoints.
4. Evaluate the ability of HER3 receptor expression levels by IHC and ERBB3 mRNA expression level to predict pathological response at surgery.
5. Evaluate Ki67 IHC after 21 days of treatment, and its ability to predict pathological response at surgery and other response endpoints.
6. Describe the safety and tolerability of HER3-DXd with or without ET vs CT in the neoadjuvant setting
7. Assess the quality of life of participants treated with HER3-DXd (either alone or in combination with letrozole) and CT.

Conditions and MedDRA coding

treatment naïve patients with HR+/HER2-negative high-risk early breast cancer.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Signed ICF
2. Male/female . At least 18 years old
3. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed, Stage II to stage IIIB breast cancer, Absence of distant metastasis. At least 1 lesion ≥ 10 mm by MRI
4. ER-positive and/or PgR-positive and HER2-negative tumor
5. Ki67 IHC % ≥ 20% locally assessed and/or high genomic risk (defined by gene signature): Oncotype DX® RS ≥ 26, Mammaprint® = Risk of Recurrence High Endopredict® = High Risk or Prosigna® ROR ≥ 60.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7. Breast cancer eligible for primary surgery.
8. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor for biomarker analysis.
9. Eligible for neoadjuvant chemotherapy
10. Adequate hematologic and end-organ function
11. willing and able to comply with trial procedures.
12. Women of childbearing potential must have confirmed negative serum pregnancy test
13. Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the time of final study drug administration.
14. Women of CBP must be willing to use highly effective methods of contraception.
15. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception and fetal protection for the duration of neoadjuvant treatment phase and after the last dose of treatment according to protocol.
16. Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration.
17. Postmenopausal or pre-menopausal
18. Patients must have the ability to swallow oral medication.
19. Baseline LVEF ≥ 50%

Exclusion criteria 24

1. Metastatic (Stage IV) breast cancer.
2. Bilateral invasive breast cancer.
3. Any treatment for the currently diagnosed BC prior to enrollment.
4. Patients in whom a primary tumor excisional biopsy was performed
5. Prior treatment with a HER3 antibody, topoisomerase I inhibitor, with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., DS-8201) and with a govitecan derivative (e.g., IMMU- 132).
6. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
7. Medical history of clinically significant lung diseases (e.g., interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period.
8. Major surgical procedure or significant traumatic injury within 28 days prior to randomization.
9. Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol.
10. Patients with a history of any malignancy are ineligible (some exception detailed in protocol)
11. Current severe, uncontrolled systemic disease or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol
12. Concurrent, serious, uncontrolled infections or current known infection with HIV or active hepatitis B and/or hepatitis C
13. History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with ICF.
14. Known hypersensitivity to either the drug substance components or inactive ingredients in the drug product or history of severe hypersensitivity reactions to other monoclonal antibodies.
15. History of exposure to cumulative anthracycline
16. Any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening.
17. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement.
18. Has unresolved toxicities from previous anticancer therapy
19. Non-eligible for taxanes therapy.
20. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1.
21. Evidence of any leptomeningeal disease.
22. Has clinically significant corneal disease.
23. Female subject who is pregnant or breastfeeding or intends to become pregnant during the study.
24. Subjects who are currently receiving chloroquine or hydroxychloroquine. A washout period of > 14 days is required prior to randomization or Cycle 1 Day 1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of pCRBL (ypT0/is ypN0) at surgery, defined as the complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination

Secondary endpoints 13

1. Rate of Residual cancer burden (RCB) category status (0, I, II, III) assessed by a local pathologist at surgery according to the MD Anderson Cancer Center recommendations.
2. pCRB defined as the complete absence of invasive carcinoma in the breast on histological examination after treatment, irrespective of in situ carcinoma in the breast.
3. Tumor overall objective response rate (ORR), defined as the proportion of subjects with a Partial Responses (PR) or a Complete Responses (CR) according to RECIST v1.1, as per Investigator's assessments by breast MRI before treatment and pre-surgery.
4. iDFS rate at 3 years follow-up
5. iDFS rate at 5 years follow-up
6. Change in CelTIL score from baseline to C2D1.
7. The Correlation of CelTIL changes from baseline to C2D1 with: pCR, RCB, ORR and iDFS.
8. The correlation of pCR with both HER3 receptor expression levels by IHC at baseline and ERBB3 mRNA expression level by gene expression at baseline.
9. The correlation of pCR with changes of HER3 receptor expression levels by IHC and ERBB3 mRNA expression level by gene expression between baseline and C2D1.
10. Change in Ki67 IHC from baseline to C2D1.
11. and correlation of Ki67 IHC changes from baseline to C2D1 with: pCR, RCB, ORR and iDFS.
12. Type, incidence, severity (as graded by the NCI CTCAE v. 5.0), seriousness, moment of onset, duration and attribution to the study medications of TEAEs, AESI and any laboratory abnormalities.
13. Change from baseline in EORTC QLQ-C30 and EORTC QLQ BR23 scores.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Solti Group

Sponsor organisation

Solti Group

Address

Calle Balmes 89 Planta 1 Puerta 2

City

Barcelona

Postcode

08008

Country

Spain

Scientific contact point

Organisation

Solti Group

Contact name

SOLTI Start-Up Group

Public contact point

Organisation

Solti Group

Contact name

SOLTI Start-Up Group

Locations

1 EU/EEA country · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

4 submissions — initial application plus substantial / non-substantial modifications