DS-9606a for Cancer

Not currently recruiting at 9 trial locations

Overseen By Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo, Inc.

Must not be taking: Corticosteroids

Disqualifiers: CNS metastases, Invasive malignancy, Heart failure, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DS-9606a, an experimental drug, to determine its safety and tolerability in people with advanced solid tumors, such as ovarian or pancreatic cancer. The trial has two parts: one part tests increasing doses to find a safe level, and the other tests the optimal dose in people with advanced ovarian cancer. Suitable candidates have cancers that have worsened with standard treatments or cannot undergo those treatments and have either advanced ovarian cancer or other specific advanced cancers. 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 mentions an 'adequate treatment washout period' before starting the study treatment, which suggests you may need to stop certain medications. However, the specific medications or duration are not detailed, so it's best to discuss this with the trial team.

Is there any evidence suggesting that DS-9606a is likely to be safe for humans?

Research has shown that DS-9606a has promising safety results in early studies. In one study, 53 patients who had already tried many treatments received DS-9606a. These patients tolerated the drug well, experiencing few serious side effects, which is a positive sign for safety.

However, since DS-9606a remains in early trials, information about its safety is limited. More side effects may become apparent as more people use it. Being in the early phase of testing means researchers are still determining the best and safest dose. Prospective trial participants should discuss any concerns with the research team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for ovarian cancer, which typically involves chemotherapy and targeted therapies like PARP inhibitors, DS-9606a is unique because it uses a novel active ingredient to specifically target cancer cells. Researchers are excited about this treatment because it offers a different mechanism of action, potentially leading to fewer side effects and improved effectiveness. Additionally, DS-9606a is administered intravenously, which allows for precise dosing and controlled delivery every three weeks, possibly enhancing patient outcomes.

What evidence suggests that DS-9606a might be an effective treatment for advanced solid tumors?

Research shows that DS-9606a has promising early results for treating certain cancers. One study found that patients with ovarian cancer had a 33.3% objective response rate (ORR), meaning their tumors shrank or disappeared. Participants in this trial will receive DS-9606a, which targets a protein called CLDN6, often found in solid tumors, to deliver cancer-fighting drugs directly to the tumor cells. This method shows encouraging results, especially in patients who have already undergone many treatments. While more information is needed, early findings suggest DS-9606a could effectively treat cancers with CLDN6. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Director

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including ovarian and germ cell cancers, who are in good physical condition (ECOG score of 0 or 1) can join. They must have a life expectancy over 3 months, proper heart function, and agree to contraception. Those with brain metastases treated successfully may qualify; however, individuals with recent serious heart issues or uncontrolled infections cannot participate.

Inclusion Criteria

You are expected to live for at least 3 more months.

I have ovarian cancer.

I am fully active or can carry out light work.

Exclusion Criteria

Your heart's electrical activity shows a QT interval that is too long based on multiple ECG readings.

I have had serious heart issues, including heart failure or irregular heartbeat needing treatment.

I have not had a heart attack or unstable chest pain in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive an intravenous (IV) dose of DS-9606a starting at 0.016 mg/kg every 3 weeks to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE)

Varies

Every 3 weeks

Dose Expansion

Participants with ovarian cancer receive an intravenous (IV) dose of DS-9606a at the recommended dose for expansion (RDE) every 3 weeks to further explore safety and tolerability and assess the overall response rate

Varies

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DS-9606a

Trial Overview The trial is testing DS-9606a's safety for patients with various advanced solid tumors. It will involve participants providing tissue samples before and during treatment to assess the drug's effects on their cancer.

How Is the Trial Designed?

Group I: Dose Expansion: DS-9606a Experimental Treatment 1 Intervention

Participants with ovarian cancer who will receive an intravenous (IV) dose of DS9606a at the recommended dose for expansion (RDE) every 3 weeks.

Group II: Dose Escalation: DS-9606a Experimental Treatment 1 Intervention

Participants who will receive an intravenous (IV) dose of DS9606a starting at 0.016 mg/kg every 3 weeks.

Who Is Running the Clinical Trial?

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

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

Published Research Related to This Trial

A 73-year-old male with recurrent non-small-cell lung cancer achieved a complete response after receiving a chemotherapy regimen of vinorelbine and platinum agents (cisplatin and carboplatin), demonstrating the efficacy of this treatment approach.

The patient experienced manageable adverse reactions, including grade 3 neutropenia and grade 2 alopecia, indicating that while the treatment was effective, it also had significant side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin/carboplatin]. Suzuki, H., Shirane, K., Nasu, H., et al.[2018]

In a study of 52 patients with advanced colorectal cancer, the combination of S-1 and cisplatin (CDDP) resulted in a 36.4% overall response rate, indicating promising efficacy, especially in patients who had not received prior chemotherapy (50% response rate).

The treatment showed acceptable toxicity levels, with median survival of 555 days and median progression-free survival of 183 days, suggesting that S-1 combined with CDDP could be a viable standard therapy for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy of S-1 and CDDP for patients with colorectal cancer. Uchida, K., Hayashi, K., Kuramochi, H., et al.[2018]

In a phase 1 study involving 60 patients with relapsed B-cell non-Hodgkin lymphoma, the anti-CD79B antibody-drug conjugate DCDS0780A showed a response rate of 47%, with 28% achieving complete responses, indicating its potential efficacy as a treatment option.

Despite the promising antitumor activity, the study noted significant ocular toxicities at higher doses, which limited dose intensity and suggested that the current TDC format may not expand the therapeutic index for targeting CD79B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD79B Antibody-Drug Conjugate DCDS0780A in Patients with B-Cell Non-Hodgkin Lymphoma: Phase 1 Dose-Escalation Study. Herrera, AF., Patel, MR., Burke, JM., et al.[2023]

In a phase I study involving 84 patients with incurable cancers, PX-866 was found to be well tolerated, with the maximum tolerated doses being 12 mg for intermittent dosing and 8 mg for continuous dosing, primarily causing gastrointestinal side effects like diarrhea.

The study demonstrated that PX-866, an irreversible inhibitor of PI3K, led to stable disease in 53% of patients on a continuous dosing schedule, indicating potential antitumor activity, especially with prolonged treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter phase I trial of PX-866, an oral irreversible phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors. Hong, DS., Bowles, DW., Falchook, GS., et al.[2021]

CLDN6-23-ADC is a novel antibody-drug conjugate that selectively targets the CLDN6 protein, which is highly expressed in ovarian and endometrial cancers but not in normal adult tissues, making it a promising therapeutic option.

In preclinical studies, CLDN6-23-ADC demonstrated significant antitumor efficacy, leading to robust tumor regressions and improved survival in mouse models of CLDN6-positive cancers, and it is currently being evaluated in a phase I clinical trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy of the Antibody-Drug Conjugate CLDN6-23-ADC for the Treatment of CLDN6-Positive Solid Tumors. McDermott, MSJ., O'Brien, NA., Hoffstrom, B., et al.[2023]

Acquired resistance to antibody-drug conjugates (ADCs) containing pyrrolobenzodiazepine (PBD) dimers, such as ADCT-301 and ADCT-402, was established in cell lines, showing resistance levels of approximately 3,000-fold for ADCT-301 in Karpas-299 cells, indicating significant challenges in treatment efficacy.

The study identified specific ATP-binding cassette transporters, particularly ABCG2 and ABCC2, as key players in the mechanism of resistance, suggesting that these transporters could serve as biomarkers for resistance and inform future drug combination strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Specific ATP-Binding Cassette Transporters in the Acquired Resistance to Pyrrolobenzodiazepine Dimer-Containing Antibody-Drug Conjugates. Corbett, S., Huang, S., Zammarchi, F., et al.[2021]

In a study of 188 stage II or III colorectal cancer patients, the combination of daily divided dose cisplatin and fluorouracil (DDD-FP) significantly improved 5-year disease-free survival (DFS) and overall survival (OS) rates in colon cancer patients compared to fluorouracil alone, with DFS at 93.5% and OS at 95.7% for DDD-FP versus 76.9% and 82.2% for 5-FU alone.

The DDD-FP regimen was found to be safe, as there were no significant differences in severe toxicities (grade 3-4) between the two treatment groups, indicating that this combination therapy is a feasible option for adjuvant treatment in resected colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: a prospective randomized trial. Hata, F., Sasaki, K., Hirata, K., et al.[2021]

ASP1650, an antibody targeting the CLDN6 protein, was tested in a phase-II trial with 19 male patients suffering from relapsed/refractory testicular germ-cell tumors, establishing a recommended phase-II dose of 1500 mg/m2 every 2 weeks without any dose-limiting toxicities.

Despite the high expression of CLDN6 in the tumors, ASP1650 did not show any clinically meaningful antitumor activity, leading to the study's early termination due to lack of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors. Adra, N., Vaughn, DJ., Einhorn, LH., et al.[2023]

In a study of 189 patients with inoperable non-small cell lung cancer, the combination of CDDP (cisplatin) and VDS (vindesine) showed the highest response rate at 26.7%, indicating a potential benefit of combining these drugs for treatment.

The study confirmed the efficacy of CDDP alone and in combination with other agents, with no deaths due to toxicity reported, suggesting that the treatments were generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II studies of a single agent and a cis-platinum-based two-drug combination in patients with non-small cell lung cancer]. Yamamoto, M., Furuse, K., Fukuoka, M., et al.[2013]

CLDN6 is a promising target for cancer treatment due to its high expression in various cancers (like ovarian and testicular) and low expression in normal adult tissues, making it a potential safe target for therapies.

Several types of anticancer drugs, including antibody-drug conjugates and CAR-T therapies, are being developed to specifically target CLDN6, which may help overcome challenges like tumor growth and chemoresistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances of Claudin6-targeting drugs in cancer therapy]. Li, G., Bi, Y., Hao, R., et al.[2023]

The newly developed m276-SL-PBD antibody-drug conjugate (ADC) targets CD276/B7-H3 and effectively eradicates large triple-negative breast cancer xenografts at doses 10- to 40-fold lower than previously tolerated doses, indicating a significant improvement in safety and efficacy.

This ADC demonstrates a cross-species reactivity and enhanced therapeutic index, suggesting that careful engineering and optimization of ADCs can lead to more effective cancer treatments with reduced side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering CD276/B7-H3-targeted antibody-drug conjugates with enhanced cancer-eradicating capability. Feng, Y., Lee, J., Yang, L., et al.[2023]

Citations

1. daiichisankyo.com daiichisankyo.com/files/news/pressrelease/pdf/202409/20240915_E.pdf

DS-9606 Shows Promising Preliminary Clinical Activity in ... Preliminary safety and efficacy results of DS-9606 were reported from the dose escalation part of the phase 1 trial in 53 heavily pretreated ...

2. onclive.com onclive.com/view/cldn6-directed-agents-generate-encouraging-early-activity-in-solid-tumors

CLDN6-Directed Agents Generate Encouraging Early ... Efficacy-evaluable patients with ovarian cancer (n = 24) in the overall population (n = 30) achieved an ORR of 33.3% (95% CI, 12.3%-45.9 ...

3. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/20833/21627/610O_Patel_DS9606-137_ESMO24_Oral_9Sep24.pdf

directed antibody–drug conjugate, in patients with tumor ... CLDN6 expression in select solid tumors​​ The results shown here are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

4. merck.com merck.com/news/raludotatug-deruxtecan-granted-breakthrough-therapy-designation-by-u-s-fda-for-patients-with-cdh6-expressing-platinum-resistant-ovarian-primary-peritoneal-or-fallopian-tube-cancers-previously-treat/

Raludotatug Deruxtecan Granted Breakthrough Therapy ... DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

5. fidelity.com fidelity.com/news/article/default/202510190845BIZWIRE_USPR_____20251019_BW170882

Raludotatug Deruxtecan Demonstrated Clinically ... An objective response rate of 50.5% was observed with raludotatug deruxtecan across all dose levels in these patients in the phase 2 part of ...

6. fidelity.com fidelity.com/news/article/default/202510190900BIZWIRE_USPR_____20251019_BW911815

DS-3939 Shows Promising Preliminary Clinical Activity in ... Preliminary safety and efficacy results of DS-3939 were reported from the dose escalation part of the phase 1/2 trial in 64 patients with ...