SAIL66 for Solid Tumors

Recruiting at 9 trial locations

Overseen By Clinical trials information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Chugai Pharmaceutical

Disqualifiers: CNS disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

231 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1 dose-escalation and expansion study that will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of SAIL66 in patients with CLDN6-positive locally advanced or metastatic solid tumors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is the drug SAIL66 different from other treatments for solid tumors?

SAIL66 may be unique in its approach to targeting the p53 pathway, which is often altered in cancer cells, potentially offering a novel mechanism to reactivate this tumor-suppressor gene and enhance the effectiveness of cancer treatment. ^{1 2 3 4 5}

Research Team

Sponsor Chugai Pharmaceutical Co. Ltd

Principal Investigator

[e-mail]

Eligibility Criteria

Adults over 18 with CLDN6-positive advanced or metastatic solid tumors can join this trial. They must be in good physical condition, meaning they're fully active or have some symptoms but can still do light work (ECOG PS of 0 or 1). A tumor sample for review is also required.

Inclusion Criteria

My tumor is CLDN6 positive.

I am fully active or can carry out light work.

Exclusion Criteria

I have pain from my cancer that isn't relieved by treatment.

I do not have uncontrolled fluid buildup in my chest, heart, or abdomen.

Intending to become pregnant or breastfeed during the study and within 3 months after the last dose of SAIL66 or tocilizumab, whichever is longer

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive SAIL66 as IV infusions at escalated doses, with or without obinutuzumab premedication

18 weeks

Weekly or tri-weekly visits

Expansion

Participants receive SAIL66 at the recommended dose to evaluate safety and efficacy

18 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• SAIL66

Trial Overview The study tests SAIL66's safety and how well it works in patients. It starts by giving small doses to a few people and slowly increasing the amount. Researchers will watch how the body reacts to it (PK/PD) and if it helps shrink the tumors.

Participant Groups

Group I: QW Dose Escalation part with/without obinutuzumab premedication Experimental Treatment 2 Interventions

Patients will receive SAIL66 as a weekly IV infusion at escalated doses, with or without obinutuzumab premedication.

Group II: Q3W Dose Escalation part Experimental Treatment 1 Intervention

Patients will receive SAIL66 as tri-weekly IV infusions at escalated doses.

Group III: Expansion part Experimental Treatment 1 Intervention

Patients will receive SAIL66 as a IV infusion at the recommended dose.

Who Is Running the Clinical Trial?

Chugai Pharmaceutical

Lead Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Findings from Research

Gene therapy using wild-type p53 delivered by adenovirus vectors is widely used in China and represents a promising approach to target cancer cells that have inactivated p53 functions.

New strategies, including oncolytic viruses and small molecules that activate p53, are being developed to enhance cancer treatment efficacy while potentially protecting normal cells, indicating a shift towards more targeted and safer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

p53-based cancer therapy. Lane, DP., Cheok, CF., Lain, S.[2022]

A novel zebrafish model was developed to study Ewing sarcoma, allowing for effective screening of treatments and quantification of tumor progression, particularly focusing on the EWSR1-FLI1 fusion protein.

Combining Nutlin-3, which reactivates the p53 pathway, with YK-4-279, which blocks EWSR1-FLI1 activity, showed enhanced inhibition of tumor growth in TP53 wild-type Ewing sarcoma cells, suggesting a promising therapeutic strategy for this subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ewing sarcoma inhibition by disruption of EWSR1-FLI1 transcriptional activity and reactivation of p53. van der Ent, W., Jochemsen, AG., Teunisse, AF., et al.[2019]

TP53 is a crucial tumor suppressor gene that, when mutated, can lead to both loss-of-function and gain-of-function effects, contributing to cancer progression and metastasis, making it a key target for cancer therapies.

Current strategies for targeting TP53 in cancer treatment include enhancing p53 activity, restoring p53 pathway function in tumors with mutations, utilizing p53 in immunotherapy, and exploring combination therapies that target both wild-type and mutant p53.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer. Zhang, S., Carlsen, L., Hernandez Borrero, L., et al.[2022]

The combination of the YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition significantly enhances the immune response against Ewing sarcoma (EwS), leading to increased viral replication and tumor cell destruction in both laboratory and animal models.

This treatment approach not only improves local tumor control but also boosts systemic immunity, as evidenced by enhanced T-cell activation and improved survival rates in preclinical studies, suggesting strong potential for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Oncolytic Adenovirus XVir-N-31 Joins Forces with CDK4/6 Inhibition Augmenting Innate and Adaptive Antitumor Immunity in Ewing Sarcoma. Schober, SJ., Schoening, C., Eck, J., et al.[2023]

Sustained mutant p53 is essential for the maintenance of tumors, indicating its critical role in cancer progression.

Targeting mutant p53 presents a promising therapeutic strategy for cancer treatment, as it could disrupt tumor survival mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Destabilization of Mutant p53 Proteins Suppresses Tumor Growth. [2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

p53-based cancer therapy. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ewing sarcoma inhibition by disruption of EWSR1-FLI1 transcriptional activity and reactivation of p53. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The Oncolytic Adenovirus XVir-N-31 Joins Forces with CDK4/6 Inhibition Augmenting Innate and Adaptive Antitumor Immunity in Ewing Sarcoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Destabilization of Mutant p53 Proteins Suppresses Tumor Growth. [2015]