DS-1471a for Cancer

No longer recruiting at 4 trial locations

Overseen By Japanese sites only: Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo Co., Ltd.

Must not be taking: Chronic steroids

Disqualifiers: CNS metastases, ILD, cardiovascular disease, autoimmune, 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 treatment called DS-1471a for individuals with advanced or metastatic solid tumors. The main goal is to assess the safety and effectiveness of DS-1471a against these challenging cancers. Participants will receive the treatment through an IV, and the trial aims to determine the optimal dose. This trial suits those who have exhausted other treatments or have no remaining options. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it mentions that an inadequate treatment washout period (time without taking certain medications) before starting the study treatment is a reason for exclusion. It's best to discuss your current medications with the trial team to understand any specific requirements.

Is there any evidence suggesting that DS-1471a is likely to be safe for humans?

Research has shown that DS-1471a, a new treatment for advanced or spreading solid tumors, has undergone lab testing. These studies found that starting with a dose of 1 mg/kg was safe, leading to its selection for the first human trials, which indicates initial confidence in its safety.

Since DS-1471a is in the early stages of human testing, detailed safety information from participants is not yet available. Early trials primarily focus on assessing safety and determining the right dose. Researchers closely monitor the treatment to evaluate participant tolerance and carefully record any side effects.

In summary, while lab studies suggest a safe starting dose, real-world data from humans is still being gathered to confirm safety. Participants in this trial will provide important information about how well DS-1471a is tolerated in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about DS-1471a because it offers a novel approach to treating cancer, particularly for patients with locally advanced or metastatic tumors. Unlike traditional chemotherapy that attacks both healthy and cancerous cells, DS-1471a is designed to specifically target tumor cells, potentially minimizing damage to normal tissue and reducing side effects. Additionally, DS-1471a is administered intravenously, allowing for direct delivery into the bloodstream, which may enhance its effectiveness in reaching and treating tumors. This targeted approach and delivery method set DS-1471a apart from existing treatments, offering hope for improved outcomes and better quality of life for patients.

What evidence suggests that DS-1471a might be an effective treatment for cancer?

Research has shown that DS-1471a, a new treatment under study in this trial, may help fight cancer. In early lab studies, DS-1471a reduced tumor growth by more than half in 7 out of 18 models made from patient tumors, suggesting it could work against different types of tumors. The treatment stops CD147 from aiding tumor growth. Early results indicate strong potential to combat cancer, offering hope for people with advanced or spreading solid tumors. Participants in this trial will receive DS-1471a in various dose escalation and expansion cohorts to determine its effectiveness and safety. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or metastatic solid tumors that have not responded to standard treatments or where no standard treatment exists. Participants must be able to provide tumor tissue samples, have a life expectancy of at least 3 months, and an ECOG performance status of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but can do light work).

Inclusion Criteria

I have a tumor that can be measured on a scan.

I can provide a sample of my tumor for testing.

Sign and date the informed consent form (ICF)

Exclusion Criteria

I have severe lung problems due to other lung diseases.

Has an inadequate treatment washout period prior to start of study treatment (Cycle 1 Day 1) as prespecified in the protocol

I do not have active or uncontrolled hepatitis, or my hepatitis B is controlled with medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive intravenous DS-1471a to evaluate safety and determine the maximum tolerated dose

Multiple cycles of 28 days each

Cycle 1 (Days 1, 2, 4, 8, 15, and 22), Cycle 2 (Day 1), Cycle 3 (Days 1, 2, 4, 8, 15, and 22), Cycles 4, 6, and 8 (Day 1)

Dose Expansion

Participants receive DS-1471a at the maximum tolerated dose to further assess efficacy and safety

Multiple cycles of 28 days each

Cycle 1 (Days 1 and 8), Cycle 2 and 3 (Day 1), and Cycle 4 and every 2 cycles thereafter (Day 1)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• DS-1471a

Trial Overview The study is testing DS-1471a, a new potential cancer therapy. It will evaluate the safety, how well it works against cancer (efficacy), how the body processes it (pharmacokinetics), and whether the body develops resistance to it (immunogenicity) in patients with advanced solid tumors.

How Is the Trial Designed?

Group I: Part 2, Dose Expansion (Tumor-specific Cohort 3): DS-1471a Experimental Treatment 1 Intervention

Participants will receive intravenous DS-1471a at the maximum tolerated dose and/or recommended dose for expansion as established in Part 1 Dose Escalation.

Group II: Part 2, Dose Expansion (Tumor-specific Cohort 2): DS-1471a Experimental Treatment 1 Intervention

Participants will receive intravenous DS-1471a at the maximum tolerated dose and/or recommended dose for expansion as established in Part 1 Dose Escalation.

Group III: Part 2, Dose Expansion (Tumor-specific Cohort 1): DS-1471a Experimental Treatment 1 Intervention

Participants will receive intravenous DS-1471a at the maximum tolerated dose and/or recommended dose for expansion as established in Part 1 Dose Escalation.

Group IV: Part 1, Dose Escalation Cohort 6: DS-1471a Experimental Treatment 1 Intervention

Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.

Group V: Part 1, Dose Escalation Cohort 5: DS-1471a Experimental Treatment 1 Intervention

Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.

Group VI: Part 1, Dose Escalation Cohort 4: DS-1471a Experimental Treatment 1 Intervention

Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.

Group VII: Part 1, Dose Escalation Cohort 3: DS-1471a Experimental Treatment 1 Intervention

Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.

Group VIII: Part 1, Dose Escalation Cohort 2: DS-1471a Experimental Treatment 1 Intervention

Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.

Group IX: Part 1, Dose Escalation Cohort 1: DS-1471a Experimental Treatment 1 Intervention

Participants with locally advanced or metastatic tumors will receive intravenous DS-1471a.

Who Is Running the Clinical Trial?

Daiichi Sankyo Co., Ltd.

Lead Sponsor

Trials

116

Recruited

49,200+

Published Research Related to This Trial

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

A follow-up program involving pharmacists for outpatients treated with oral antineoplastic agents (OAA) showed a reduction in severe adverse events (AEs) and major drug interactions compared to patients who were not monitored, indicating improved safety in the intervention group.

The study included 249 patients over a 6-month period, revealing that while AEs were still common, the intervention group experienced fewer severe AEs and had better monitoring of drug interactions, particularly with medications like erlotinib and gefitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy follow-up of key points in the safety of oral antineoplastic agents. Escudero-Vilaplana, V., Ribed, A., Romero-Jimenez, RM., et al.[2018]

Combining anti-PD-1 or anti-PD-L1 immunotherapy with platinum-based chemotherapy significantly improves outcomes for patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), based on a systematic review of 9 randomized studies.

While immune-mediated adverse events (AEs) and infusion reactions were more common with the combination therapy, there were no unexpected toxicities, indicating that the treatment is generally safe and manageable with appropriate monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. Hoffner, B., Leighl, NB., Davies, M.[2020]

Adjuvant therapy with PD-1/PD-L1 inhibitors significantly improves overall survival (OS) and disease-free survival (DFS) in cancer patients, based on a meta-analysis of six randomized controlled trials involving 4,436 participants.

While these treatments offer substantial survival benefits, they are also associated with a higher risk of severe treatment-related adverse events (≥ grade 3), indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. Mo, DC., Liang, ZY., Chen, L., et al.[2022]

In a study of 66 patients with operable stage III non-small cell lung cancer (NSCLC), the combination of Camrelizumab with Docetaxel and Cisplatin showed good overall safety, with most adverse events (AEs) being mild (grade 1-2) and only 9.1% being severe (grade 3-4).

The supervision of adverse events during neoadjuvant therapy not only helped in managing complications but also led to an improvement in patients' quality of life, indicating that careful monitoring can enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC]. Zhang, Y., Zhou, S., Tao, W., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06074705

A Study of DS-1471a In Subjects With Advanced Solid ... This first-in-human (FIH) study will assess the safety, preliminary efficacy, pharmacokinetics (PK), and immunogenicity of DS-1471a in participants with ...

2. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/20833/21627/ESMO%202024_DS-1471_Koganemaru_Poster_FINAL.pdf

A Phase 1, first-in-human study of DS-1471 in patients with ... DS-1471 injection (IP or IV) was performed on the day of group allocation (n=5 or 6 mice per group). Tumor size was measured twice weekly.

3. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/B127/730488/Abstract-B127-Novel-anti-CD147-antibody-DS-1471a

Abstract B127: Novel anti-CD147 antibody DS-1471a exerts ... Results: Seven out of 18 PDX models showed over 50% TGI with DS-1471a treatment in comparison to vehicle, regardless of gender, tumor grade, and ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02267-1/pdf

682TiP A phase I, first-in-human study of DS-1471 in ... DS-1471, a humanized IgG4 mono- clonal antibody targeting CD147, has shown preclinical antitumor activity by inhibiting complex formation between CD147 and ...

5. ctv.veeva.com ctv.veeva.com/study/a-study-of-ds-1471a-in-subjects-with-advanced-solid-tumors

A Study of DS-1471a In Subjects With Advanced Solid Tumors This first-in-human (FIH) study will assess the safety, preliminary efficacy, pharmacokinetics (PK), and immunogenicity of DS-1471a in ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02267-1/fulltext

682TiP A phase I, first-in-human study of DS-1471 in ... DS-1471, a humanized IgG4 monoclonal antibody targeting CD147, has shown preclinical antitumor activity by inhibiting complex formation between CD147 and ...

7. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/A138/730697/Abstract-A138-Preclinical-pharmacokinetic

Abstract A138: Preclinical pharmacokinetic-pharmacodynamic ... Based on preclinical PK-PD analysis and safety study of DS-1471a, the starting dose in FIH study was set to 1 mg/kg as a safe and efficacious dose.

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06074705/a-study-of-ds-1471a-in-subjects-with-advanced-solid-tumors

A Study of DS-1471a In Subjects With Advanced Solid ... This first-in-human (FIH) study will assess the safety, preliminary efficacy, pharmacokinetics (PK), and immunogenicity of DS-1471a in ...