Study of Biological Effect in Tumor Samples from Clinical Trial Patients Treated with Ds8201

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Solti Group

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Dec 2019 → ongoing

Decision date (initial)

2023-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Daiichi Sankyo Inc.

External identifiers

EU CT number

2023-508830-33-00

EudraCT number

2019-002991-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Others

To identify the optimal ERBB2 mRNA cut-point predictive of Trastuzumab Deruxtecan response in breast cancer

Secondary objectives 9

1. To identify the optimal ERBB2 mRNA cut-point predictive of Trastuzumab Deruxtecan response in all tumors
2. Evaluate the correlation of mRNA ERBB2 levels (as a continuous variable) in baseline FFPE tumor samples with overall response in the Trastuzumab Deruxtecan-treated cohorts.
3. To evaluate the association of mRNA ERBB2 levels with progression- free survival and overall survival.
4. To evaluate the association of the PAM50 intrinsic subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) with overall response, PFS and OS.
5. To evaluate the association of immune-related genes with overall response, PFS and OS.
6. To design a new gene expression signature predictive of Trastuzumab Deruxtecan benefit.
7. To evaluate the benefit of Trastuzumab Deruxtecan across somatic mutations
8. To correlate early changes in ctDNA with Trastuzumab Deruxtecan benefit
9. To identify acquired somatic mutations of resistance to Trastuzumab Deruxtecan upon progression in plasma samples

Conditions and MedDRA coding

Patients diagnosed with advanced or metastatic cancer treated with Trastuzumab Deruxtecan in the context of a clinical trial/expanded access/ compassionate use or standard treatment, irrespective of histologic type.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Women and men ≥18 years old who are starting, are receiving or have received treatment with Trastuzumab Deruxtecan (T-DXd; DS-8201a) as a treatment for metastatic/advanced cancer.
2. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. It is possible to include patients that were exitus during or after treatment by filling out the appendix 1 form and filing it into the patient's clinical chart.
3. Submission of a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block from the most recently collected tumor tissue, with an associated pathology report, for central molecular analysis and for other protocol-mandated secondary and exploratory assessments. If a newer specimen is either insufficient or unavailable, the patient may still be eligible if the patient can provide a tissue block (preferred) or is willing to consent to and undergo an additional pretreatment core or excisional biopsy (if it is assessable and the biopsy can be safely obtained). The tumor tissue should be of good quality and quantity based on total and viable tumor content.a. Acceptable samples include core needle biopsies of the deep metastatic lesion or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions or biopsies from bone metastases. b.Fine needle aspiration, brushing, cell pellet from pleural effusion and lavage samples are not acceptable.
4. Patients included before starting experimental treatment must be able and willing to provide blood sample(s).

Exclusion criteria 1

1. Not applicable

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To identify the optimal ERBB2 mRNA cut-point predictive of DS-8201 response -Correlation of mRNA ERBB2 levels (as a continuous variable) in baseline FFPE tumor samples with overall response in the DS8201a-treated cohorts.
2. Correlation of mRNA ERBB2 levels (as a continuous variable) in baseline FFPE tumor samples with overall response in the DS8201a-treated cohorts.

Secondary endpoints 7

1. To evaluate the association of mRNA ERBB2 levels with progression- free survival and overall survival.
2. To evaluate the association of the PAM50 intrinsic subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) with overall response rate, progression free survival (PFS) and overall survival (OS).
3. To evaluate the association of immune-related genes with overall response, progression free survival (PFS) and overall survival (OS).
4. To design a new gene expression signature predictive of DS8201a benefit
5. To evaluate the benefit of DS8201a across somatic mutations.
6. To correlate early changes in ctDNA with DS8201a benefit.
7. To identify acquired somatic mutations of resistance to DS8201a upon progression in plasma samples

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

Gran Via De Carles III 86 Planta 9

City

Barcelona

Postcode

08028

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 · 15 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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