STI-6643 for Advanced Cancers

Recruiting at 3 trial locations

Overseen By Mike Royal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sorrento Therapeutics, Inc.

Must not be taking: Anti-CD47, SIRPα antibodies

Disqualifiers: CNS involvement, Active infection, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 4

100 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, there are specific time requirements for stopping certain treatments before starting the trial, such as systemic anti-tumor treatments, irradiation, and immunosuppressive therapy. It's best to discuss your current medications with the trial team to see if they affect your eligibility.

What data supports the idea that STI-6643 for Advanced Cancers is an effective drug?

The available research does not provide specific data on the effectiveness of STI-6643 for Advanced Cancers. Instead, it discusses other drugs and treatments for advanced cancers, such as OSI-461 and vosaroxin, which have been studied for their safety and effectiveness. For example, vosaroxin combined with decitabine showed a 74% overall response rate in patients with acute myeloid leukemia, indicating its potential effectiveness. However, there is no direct information on STI-6643's effectiveness in the provided research. ^{1 2 3 4 5}

What safety data is available for STI-6643 in advanced cancers?

The safety data for STI-6643, also known as OSI-461, can be found in studies evaluating its use in patients with advanced solid tumors. The studies include a dose-ranging study of OSI-461, which assessed its safety and pharmacokinetics, and a phase I study that explored its combination with mitoxantrone to determine the maximum tolerated dose. These studies provide insights into the safety profile of OSI-461 in advanced cancer patients. ^{1 2 3 6 7}

Is the drug STI-6643 a promising treatment for advanced cancers?

The information provided does not mention STI-6643, so we cannot determine if it is a promising treatment for advanced cancers based on the given research articles. ^{1 2 8 9 10}

What is the purpose of this trial?

This is a first-in-human, phase 1, open-label, dose-escalation study of STI-6643 administered by intravenous infusion in subjects with a relapsed/refractory advanced solid tumor.

Research Team

Mike Royal, MD

Principal Investigator

Sorrento Therapeutics, Inc.

Eligibility Criteria

Adults with advanced solid tumors that have relapsed or are unresponsive to standard treatments can join this trial. They must have a life expectancy over 12 weeks, acceptable blood counts and organ function, and no recent other treatments or surgeries. Women of childbearing potential need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

I am a woman who can have children and have a negative pregnancy test.

I am a woman who is either postmenopausal, cannot have children, or will use birth control during and after the study.

I am a man who is either surgically sterile or will use contraception during and 30 days after the study.

Exclusion Criteria

I have not had an infection needing treatment in the last 3 days.

I do not have serious heart issues or uncontrolled high blood pressure.

I have an infection with HTLV1, HBV, or HCV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Participants receive STI-6643 intravenously with dose escalation to determine MTD and RP2D using a 3+3 study design

4 weeks

Weekly visits for 4 weeks

Therapeutic Dose Escalation

Participants continue receiving STI-6643 biweekly for Cycles 2 and up

Up to 31 months

Biweekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• STI-6643

Trial Overview The trial is testing STI-6643, an experimental drug given by IV for those with certain advanced cancers. It's the first time humans will receive it (phase 1), focusing on finding a safe dose while observing its effectiveness against tumors.

Participant Groups

Group I: STI-6643 Experimental Treatment 1 Intervention

STI-6643 will be provided in a single use 10-mL high borosilicate type 1 glass vial at a concentration of 500mg/10 mL (50 mg/mL) administered intravenously weekly for 4 weeks, then biweekly for Cycles 2 and up.

Who Is Running the Clinical Trial?

Sorrento Therapeutics, Inc.

Lead Sponsor

Trials

48

Recruited

2,000+

Findings from Research

In a phase I trial involving 33 patients with advanced solid tumors, OSI-461 was found to be well-tolerated at a recommended dose of 800 mg taken twice daily with food, which significantly increased its bioavailability.

The study identified dose-limiting toxicities such as grade 3 abdominal pain and fatigue at higher doses, but overall, the drug showed promising pharmacodynamic effects, including increased levels of pGSK-3beta, indicating its potential effectiveness in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose-ranging study of the pharmacokinetics and pharmacodynamics of the selective apoptotic antineoplastic drug (SAAND), OSI-461, in patients with advanced cancer, in the fasted and fed state. O'Bryant, CL., Lieu, CH., Leong, S., et al.[2021]

The maximum tolerated dose (MTD) of OSI-461 was determined to be 1,000 mg taken orally twice daily in combination with mitoxantrone, with the combination generally well tolerated by patients with advanced solid tumors.

Out of the patients studied, 10% experienced a partial response and 50% had stable disease, indicating that while the combination was safe, the response rates were similar to those seen with mitoxantrone alone, leading to the decision not to pursue further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone. Resta, LP., Pili, R., Eisenberger, MA., et al.[2021]

In a phase I study involving 43 patients with advanced solid tumors, MEDI-573 demonstrated a favorable safety profile with no dose-limiting toxicities and only one case of treatment-related hyperglycemia.

While MEDI-573 did not lead to any partial or complete responses in the tumors, 13 out of 39 evaluable patients showed stable disease, indicating some preliminary antitumor activity in a heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Haluska, P., Menefee, M., Plimack, ER., et al.[2021]

In a phase II trial involving 65 patients aged 60 and older with acute myeloid leukemia or myelodysplastic syndrome, the combination of vosaroxin and decitabine showed a high overall response rate of 74%, with 48% achieving complete remission.

Reducing the vosaroxin dose to 70 mg/m2 significantly decreased the incidence of severe mucositis and improved median overall survival to 14.6 months, compared to 5.5 months with the higher dose, indicating a better safety profile while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Daver, N., Kantarjian, H., Garcia-Manero, G., et al.[2019]

Panobinostat, a histone deacetylase inhibitor, shows significant synergy with gemcitabine and paclitaxel, and particularly strong synergistic effects when combined with doxorubicin and carboplatin in treating metastatic ovarian cancer cell lines.

The study utilized in vitro assays on three ovarian cancer cell lines (SK-OV3, CaOV-3, and ES-2) to identify effective drug combinations, suggesting that these combinations could enhance treatment efficacy and warrant further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. Budman, DR., Tai, J., Calabro, A., et al.[2021]

The combination of the ATR inhibitor M6620 and the TOP1 inhibitor topotecan was well tolerated in a phase I study involving 21 patients, allowing for dose escalation to the maximum planned dose, despite some instances of dose-limiting toxicities like thrombocytopenia.

This treatment showed promising efficacy, particularly in patients with platinum-refractory small-cell lung cancer, with two partial responses and several cases of stable disease lasting over three months, indicating potential for further investigation in phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors. Thomas, A., Redon, CE., Sciuto, L., et al.[2022]

The maximum tolerated dose of KOS-862, an epothilone for treating advanced solid tumors or lymphoma, was established at 100 mg/m², with manageable toxicity observed in a study involving 32 patients.

KOS-862 demonstrated a favorable pharmacokinetic profile and showed signs of clinical activity, including tumor shrinkage and stable disease in several patients, indicating its potential effectiveness in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma. Konner, J., Grisham, RN., Park, J., et al.[2021]

In a phase Ib/II clinical trial of APR-246 combined with chemotherapy for metastatic esophageal cancer, TP53 mutation status was found to be an unreliable predictor of response to the treatment, suggesting that other factors should be considered for patient selection.

The study identified SLC7A11 expression as a superior biomarker for predicting sensitivity to APR-246, indicating that it should be used to better stratify patients in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SLC7A11 Is a Superior Determinant of APR-246 (Eprenetapopt) Response than TP53 Mutation Status. Fujihara, KM., Corrales Benitez, M., Cabalag, CS., et al.[2022]

APR-246 effectively reactivates mutant p53 protein in high-grade serous ovarian cancer, showing strong synergy with cisplatin and other chemotherapy agents in primary cancer cells from patients, particularly those with TP53 mutations.

The combination of APR-246 with cisplatin significantly reduced the drug's effective concentration needed to kill cancer cells, indicating that this treatment could enhance the efficacy of chemotherapy in patients with TP53 mutant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancer. Fransson, Å., Glaessgen, D., Alfredsson, J., et al.[2021]

In a study of 20 patients with advanced gastrointestinal stromal tumors (GISTs), ecteinascidin 743 (ET-743) showed limited efficacy, with no objective responses and only two patients experiencing disease stabilization for 4 and 10 months.

The treatment was generally well-tolerated, with severe toxicities being reversible and primarily consisting of grade 3 transaminitis in 10 patients, indicating a safety profile but highlighting the primary resistance of GISTs to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors. Ryan, DP., Puchalski, T., Supko, JG., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A dose-ranging study of the pharmacokinetics and pharmacodynamics of the selective apoptotic antineoplastic drug (SAAND), OSI-461, in patients with advanced cancer, in the fasted and fed state. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone. [2021]

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

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. [2019]

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

The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. [2021]

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

Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors. [2022]

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

Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma. [2021]

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

SLC7A11 Is a Superior Determinant of APR-246 (Eprenetapopt) Response than TP53 Mutation Status. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors. [2019]