DS-1103a + T-DXd for Advanced Cancer

Not currently recruiting at 11 trial locations

Overseen By Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Myocardial infarction, ILD, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with advanced solid tumors, specifically those exhibiting certain HER2 characteristics, a protein involved in cancer growth. The goal is to determine the safety and effectiveness of this combination in treating these cancers. The treatment includes DS-1103a (an anti-SIRPα monoclonal antibody) and T-DXd. The trial consists of two groups: one for individuals with HER2-expressing or HER2-mutant tumors and another for those with specific types of breast cancer with low HER2 expression. Suitable candidates are those with advanced cancer unresponsive to current treatments and possessing HER2-related characteristics. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use chronic systemic corticosteroids or other immunosuppressive medications during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that DS-1103a, when combined with T-DXd, is generally well-tolerated in early research. This combination blocks a specific interaction, enhancing the immune system's ability to attack cancer cells. Research indicates that this approach improves the targeting of tumor cells by cancer treatments.

Initial human tests have reported no severe side effects, suggesting the treatment is reasonably safe. However, as this is an early-stage trial, more information is needed about potential side effects and overall safety. Researchers closely monitor participants to ensure their safety and manage any side effects that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of DS-1103a and T-DXd for advanced cancers because it targets tumors in a novel way. Unlike many current treatments that focus on traditional chemotherapy, DS-1103a is a targeted therapy designed to work alongside T-DXd, which is an antibody-drug conjugate. This combo is particularly promising for patients with HER2-expressing tumors, as it specifically targets HER2 proteins, potentially leading to more effective treatment outcomes. By leveraging this new mechanism of action, the treatment aims to provide a more personalized and potentially more effective option for those with advanced metastatic solid tumors.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research shows that DS-1103a blocks a specific interaction that usually helps cancer cells evade the immune system. By stopping this interaction, DS-1103a enables the immune system to attack cancer cells more effectively. In this trial, participants will receive DS-1103a combined with T-DXd, a drug that targets and kills cancer cells. Studies have found that this combination can enhance the body's ability to fight cancer, particularly in advanced solid tumors. This method shows promise for treating cancers with changes in the HER2 protein, often linked to fast-growing tumors. ^{1 2 3 5 6}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors, specifically HER2-expressing or mutated, who've had prior treatment without success. They must have measurable lesions and be in good health with proper organ function. Women of childbearing age need a negative pregnancy test and agree to birth control; men must also use birth control.

Inclusion Criteria

Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures

Presence of at least 1 measurable lesion based on computed tomography (CT) or magnetic resonance imaging (MRI)

I am a man who is sterile or my partner uses effective birth control.

Exclusion Criteria

I am pregnant, breastfeeding, or planning to become pregnant.

I am currently taking long-term steroids or other drugs that weaken my immune system.

Has a QTcF prolongation to >470 ms (females) or >450 ms (males)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive DS-1103a and T-DXd in a dose-escalating manner to assess safety and efficacy

Up to 44 months

Cycles 1, 2, and 4: Days 1, 2, 4, 8, 15; Cycle 3: Days 1, 8, 15; Cycle 5 and beyond: Day 1 (each cycle is 21 days)

Dose Expansion

Participants receive DS-1103a at the recommended dose for expansion in combination with T-DXd

Up to 44 months

Cycles 1 and 3: Days 1, 2, 4, 8, 15; Cycle 2: Days 1, 8, 15; Cycle 4 and beyond: Day 1 (each cycle is 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DS-1103a

Trial Overview The trial is testing DS-1103a combined with T-DXd for safety and effectiveness against advanced solid tumors. Participants will receive this combination therapy to see how well it works compared to current treatments.

How Is the Trial Designed?

Group I: Dose Expansion: DS-1103a + T-DXd Experimental Treatment 2 Interventions

Participants with HER2-low expressing breast cancer who will receive an IV infusion of DS-1103a at the recommended dose for expansion (RDE) in combination with T-DXd 5.4 mg/kg Q3W starting on Cycle 1 Day 1.

Group II: Dose Escalation: DS-1103a + T-DXd Experimental Treatment 2 Interventions

Participants with HER2-expressing or HER2-mutant advanced metastatic solid tumors who will receive an intravenous (IV) infusion of DS-1103a (starting dose of 100 mg) every 3 weeks (Q3W) starting on Cycle 1 Day 1. Starting on Cycle 2 Day 1 and on Day 1 of each subsequent cycle, participants will also receive T-DXd Q3W at a dose of 5.4 mg/kg.

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Lead Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In ovarian carcinoma, polyploid giant cancer cells (PGCCs) contribute to drug resistance, particularly after chemotherapy with paclitaxel, and this study highlights the role of Sirtuin1 (SIRT1) in this process.

Tumor cells with mutated SIRT1 showed increased polyploidy and reduced senescence compared to those with normal SIRT1, suggesting that cytoplasmic SIRT1 influences PGCC formation and enhances resistance to paclitaxel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoplasmic SIRT1 promotes paclitaxel resistance in ovarian carcinoma through increased formation and survival of polyploid giant cancer cells. Xu, H., Zeng, S., Wang, Y., et al.[2023]

SIRT3, a mitochondrial deacetylase, plays a crucial role in regulating reactive oxygen species (ROS) signaling, which is important for controlling cell migration and metastasis in breast cancer.

Overexpression of SIRT3 inhibits cell migration and metastasis, and its levels are inversely correlated with metastatic outcomes in human breast cancers, suggesting that enhancing SIRT3 could be a potential therapeutic strategy against cancer spread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of epithelial cell migration and Src/FAK signaling by SIRT3. Lee, JJ., van de Ven, RAH., Zaganjor, E., et al.[2018]

Short-term, low-dose treatment with Tenovin-6 (TnV6) inhibits sirtuins and induces cellular senescence in primary human fibroblasts, leading to cell cycle arrest and increased markers of senescence, such as elevated p21 levels and secretion of pro-inflammatory IL-6.

While TnV6 may have potential clinical applications for inducing senescence in certain contexts, the study warns that even non-genotoxic anticancer drugs can adversely affect healthy cells, highlighting the need for careful consideration of their broader impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of a novel model of primary human cell senescence through Tenovin-6 mediated inhibition of sirtuins. Walters, HE., Cox, LS.[2020]

Cytoplasmic SIRT1 acts as a tumor suppressor in ovarian carcinoma by inhibiting tumor cell migration and invasion, which was demonstrated through experiments with ovarian carcinoma cell lines and various assays.

The study found that mutations preventing SIRT1 from entering the nucleus led to its cytoplasmic localization, suggesting that the location of SIRT1 within the cell influences its role in tumor progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial-mesenchymal transition in ovarian carcinoma. Yang, T., Zhou, R., Yu, S., et al.[2020]

Overexpression of SIRT6 in A549 non-small cell lung cancer cells significantly inhibits cell proliferation and enhances radiosensitivity, with a sensitization enhancement ratio of 1.35 compared to control groups after X-ray irradiation.

The study demonstrated that SIRT6 overexpression leads to cell cycle arrest in the G1 phase and promotes apoptosis by increasing pro-apoptotic gene expression (Bax and Cleaved caspase-3) while decreasing anti-apoptotic gene expression (Bcl-2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization effect of overexpression of adenovirus-mediated SIRT6 on A549 non-small cell lung cancer cells. Cai, Y., Sheng, ZY., Liang, SX.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05765851

A Study of DS-1103a Combination Therapy in Participants ... DS-1103a, a recombinant humanized IgG4 anti-SIRPα antibody designed to block the SIRPα-CD47 interaction, is being developed for the treatment of advanced ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11156334/

Blockade of SIRPα-CD47 axis by anti-SIRPα antibody ... DS-1103a inhibited SIRPα-CD47 interaction and enhanced antibody-dependent cellular phagocytosis of Dato-DXd and T-DXd against human cancer cells ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e14509

Development of a quantitative systems pharmacology ... Background: DS-1103a, an anti-human signal regulatory protein α (SIRPα) monoclonal antibody (mAb), is designed to block the SIRPα-CD47 axis ...

4. researchgate.net researchgate.net/publication/381228230_Blockade_of_SIRPa-CD47_axis_by_anti-SIRPa_antibody_enhances_anti-tumor_activity_of_DXd_antibody-drug_conjugates

(PDF) Blockade of SIRPα-CD47 axis by anti- ... DS-1103a inhibited SIRPα-CD47 interaction and enhanced antibody-dependent cellular phagocytosis of Dato-DXd and T-DXd against human cancer cells ...

5. daiichisankyo.com daiichisankyo.com/files/investors/library/quarterly_result/2025/Q2/FY2025Q2_Reference_Data_E.pdf

Reference Data US HER2-low Breast Cancer (post chemo). 0.9. 0.9. (50.0%). -. -. 1.9. 1.9 ... DS-1103（anti-SIRPα antibody）. 51. Page 54. Study Name. Population.

6. careacross.com careacross.com/clinical-trials/trial/NCT05765851

A Study of DS-1103a Combination Therapy in Participants ... Summary: This study will evaluate the safety and efficacy of DS-1103a combination therapy in patients with advanced solid tumors. Detailed description: DS-1103a ...