DS-1471a for Cancer

Recruiting at 3 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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This first-in-human (FIH) study will assess the safety, preliminary efficacy, pharmacokinetics (PK), and immunogenicity of DS-1471a in participants with advanced or metastatic solid tumors.

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.

What safety data exists for DS-1471a or similar treatments in humans?

The safety of treatments similar to DS-1471a, such as PD-1/PD-L1 inhibitors, has been evaluated in cancer patients. Common side effects include diarrhea, rash, dry skin, nail issues, and fatigue, but these treatments are generally considered safe when managed properly. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC]. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy follow-up of key points in the safety of oral antineoplastic agents. [2018]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. [2022]

5. England 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. [2022]