Phase 2 Study of HER3-DXd in Locally Advanced or Metastatic Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Jul 2024 → ongoing

Decision date (initial)

2024-05-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc.

External identifiers

EU CT number

2023-507641-29-00

ClinicalTrials.gov

NCT06172478

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Dose response, Pharmacokinetic, Others

To assess the efficacy of HER3-DXd monotherapy

Secondary objectives 4

1. To assess the safety and tolerability of HER3-DXd monotherapy
2. To further assess the efficacy of HER3 DXd monotherapy
3. To evaluate the PK of HER3-DXd monotherapy
4. To evaluate HER3 protein expression in tumor tissue and its relationship with HER3-DXd efficacy

Conditions and MedDRA coding

Locally Advanced or Metastatic Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Sign and date the ICF, prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all subjects to meet the baseline tumor tissue requirement.
2. Subject aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old
3. Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) (see details on page 99)
4. Has ≥1 measurable lesion on computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST v1.1 by investigator assessment. Prostate cancer subjects with bone only disease may be eligible.
5. Provides a pretreatment tumor tissue sample that meets 1 of the collection requirements (see details on page 103)
6. Has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at screening
7. Has adequate bone marrow reserve and organ function based on local laboratory data within 7days prior to Cycle 1 Day (see table starting on page 103)
8. If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control upon enrolment, during the Treatment Period, and for 7 months following the last dose of study drug (see table on page 103).
9. 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 ≥7 months after the final study drug administration.
10. A male, subject capable of producing sperm is eligible to participate if he agrees to the following, during the intervention period, and for at least the time needed the trial intervention. The length of time required to continue contraception after last dose for the trial intervention is ≥4 months(see details on page 103)
11. Male subjects must not freeze or donate sperm starting at screening and throughout the study period and ≥4 months after the final study drug administration.
12. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
13. Sub study: Participant is taking part in the Phase II open-label study.
14. Sub study: Participant provides consent to participate in the interview sub-study via the Study Informed Consent Form (ICF).
15. Sub study: Participant consents to be audio recorded.
16. Sub study: Participant resides in Belgium, Spain, Japan, Korea, Taiwan, continental US (Puerto Rico is excluded), UK, Australia, Canada, Czech Republic, Germany, Hungary, Italy, Norway, The Netherlands
17. Sub study: Participant can communicate and read fluently in country local language including Belgian-French, Spanish, Japanese, Korean, Taiwanese-Mandarin, Canadian-French, Czech, German, Hungarian, Italian, Norwegian, Dutch or English.
18. Sub study: Participant is physically able to participate in a one-on-one, approximately 45-minute interview (conducted in one sitting) using an internet-enabled computer or other device (such as a tablet) with screensharing / screen-viewing capabilities

Exclusion criteria 23

1. Has HER2-positive gastric cancer as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations)
2. Has nasopharyngeal cancer
3. Has mucosal or uveal melanoma
4. Has a history of (non- infectious) ILD that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging during screening.
5. Has clinically severe respiratory compromise (based on the investigator’s assessment) resulting from intercurrent pulmonary illnesses (see details on page 104)
6. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone daily or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study
7. Has any history of or evidence of current leptomeningeal disease
8. Has clinically significant corneal disease
9. Has evidence of clinically active spinal cord compression or brain metastases, defined as being symptomatic or untreated, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and not requiring treatment with corticosteroids or anticonvulsants) may be included in the study but must have a stable neurologic status for ≥4 weeks prior to Cycle 1 Day 1. Subjects with asymptomatic brain metastases and treated with anticonvulsants as prophylaxis are able to enroll.
10. Had inadequate washout period prior to Cycle 1 Day 1 (see details on page 105)
11. Had prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
12. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved by the National Cancer Institute – Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0) to Grade ≤1 or baseline (see details on page 105).
13. Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following: a. Adequately treated nonmelanoma skin cancer and adequately treated thin primary melanoma <1 mm. b. Adequately treated intraepithelial carcinoma of the cervix c. Any other curatively treated in situ disease. d. Early prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) not requiring treatment
14. Has uncontrolled or significant cardiovascular disorder prior to Cycle 1 Day 1 (see details on page 106)
15. Has active or uncontrolled hepatitis C virus infection infection (see details on page 106).
16. Has uncontrolled HIV1/2 infection (see details on page 107).
17. Has active or uncontrolled HBV infection (see details on page 107).
18. Has any evidence of severe or uncontrolled diseases (eg, active bleeding diatheses, active serious infection) psychiatric illness/social situations, geographical factors, substance abuse, or other factors that, in the investigator’s opinion, make it high risk for the subject to participate in the study or that would jeopardize compliance with the protocol.
19. Has known hypersensitivity to either the drug substance or inactive ingredients in the drug product.
20. Is a female subject who is pregnant or breastfeeding or intends to become pregnant during the study
21. Has prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator’s opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results
22. Has previously received topoisomerase-1 inhibitors (e.g., irinotecan treatment in the advanced or metastatic disease)
23. Sub study: Participant is unable to adhere to the requirements of the interview sub-study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary endpoint of the study is ORR as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). for all cohorts except Prostate cancer cohort
2. For Prostate Cohort only:The PE is PSA50. Changes in PSA have been shown to correlate with OS, and this EP will allow for timely understanding of the antitumor activity in parallel with available safety endpoints. PSA50 response rate, defined as the proportion of patients with a ≥50% decrease in PSA level from baseline to the lowest postbaseline PSA result, confirmed by a consecutive PSA assessment at least 3 weeks later has been used in other clinical studies in prostate cancer

Secondary endpoints 13

1. TEAEs and other safety parameters during the study
2. Duration of response (DoR)
3. Clinical benefit rate (CBR)
4. Disease control rate (DCR)
5. Time to response (TTR)
6. Progression-free survival (PFS) evaluated by the investigator per RECIST v1.1
7. Overall survival (OS), including Prostate cancer cohort
8. PK endpoints, including Prostate cancer cohort
9. Correlation between HER3 protein expression at baseline (as determined by HER3 IHC assay) and efficacy, , including Prostate cancer cohort
10. For Prostate cohort only: rPFS (PCWG3)
11. For Prostate cohort only: PSA30 response rate
12. For Prostate cohort only: Time to first subsequent anticancer therapy (TFST)
13. For Prostate cohort only: Time to first symptomatic skeletal-related event (SSRE)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 5

Locations

8 EU/EEA countries · 46 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 137 files

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

Application history

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