INV-9956 for Prostate Cancer

Recruiting at 5 trial locations

Overseen By Yi Zhu, MD, MBA

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Shenzhen Ionova Life Sciences Co., Ltd.

Must be taking: GnRH analogue

Disqualifiers: Crohn's, Diabetes, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

66 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1a, first-in-human, open-label dose-escalation study to determine the RDR and/or MTD, and to assess the DLT of INV-9956. The safety, tolerability, PK/PD, and preliminary antitumor activity of INV-9956 will be assessed in adult patients with advanced mCRPC.

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

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing androgen deprivation therapy is required, so you should continue that treatment.

What safety data exists for INV-9956 (enzalutamide) in humans?

Enzalutamide, used for prostate cancer, has been associated with severe thrombocytopenia (low platelet count) and seizures in some cases. It is important to discuss potential side effects with your doctor. ^{1 2 3 4 5}

How does the drug INV-9956 differ from other prostate cancer treatments?

The drug INV-9956 is unique because it may involve a novel mechanism or approach not detailed in the available research, as there is no direct information about it. However, similar treatments like insulin potentiation therapy (IPT) combined with low-dose chemotherapy have shown promise in managing castration-resistant prostate cancer with minimal side effects, suggesting that INV-9956 might also offer a new way to treat this condition. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adult males with advanced metastatic castration-resistant prostate cancer who've had prior chemotherapy and hormonal therapy. They must be able to swallow pills, have a life expectancy over 3 months, and maintain specific health criteria like normal blood clotting and organ function.

Inclusion Criteria

INR ≤1.5

I've had taxane chemotherapy and hormonal therapy for my cancer.

Has a life expectancy of >3 months

Exclusion Criteria

Clinically significant abnormality in serum potassium and sodium

My diabetes is not well-managed.

I do not have any active or unstable heart or brain blood vessel problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Stage 1 involves dose escalation to determine the maximum tolerated dose (MTD) and recommended dose range (RDR) of INV-9956, co-administered with dexamethasone and fludrocortisone acetate.

4 weeks

Multiple visits for dose escalation and monitoring

Dose Expansion

Stage 2 involves dose expansion to further assess the safety, tolerability, and preliminary antitumor activity of INV-9956 at the determined dose levels.

12 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of radiographic progression-free survival and overall response rate.

12 months

Treatment Details

Interventions

• INV-9956

Trial Overview INV-9956 is being tested in this early-phase trial to find the right dose that's safe but effective. Researchers will look at how the body processes it, its safety profile, and any signs of it fighting the cancer.

Participant Groups

Group I: Stage 3 INV-9956 Dose escalation beyond the optimal dose - Dose level 6 Experimental Treatment 1 Intervention

INV-9956 Dose escalation Dose level 6 is co-administered with dexamethasone and fludrocortisone acetate

Group II: Stage 3 INV-9956 Dose escalation beyond the optimal dose - Dose level 5 Experimental Treatment 1 Intervention

INV-9956 Dose escalation Dose level 5 is co-administered with dexamethasone and fludrocortisone acetate

Group III: Stage 3 INV-9956 Dose escalation beyond the optimal dose - Dose level 4 Experimental Treatment 1 Intervention

INV-9956 Dose escalation Dose level 4 is co-administered with dexamethasone and fludrocortisone acetate

Group IV: Stage 2 INV-9956 Dose expansion - Dose Level 2 Experimental Treatment 1 Intervention

INV-9956 Dose expansion Dose Level 2 is co-administered with dexamethasone and fludrocortisone acetate

Group V: Stage 2 INV-9956 Dose expansion - Dose Level 1 Experimental Treatment 1 Intervention

INV-9956 Dose expansion Dose Level 1 is co-administered with dexamethasone and fludrocortisone acetate

Group VI: Stage 1 INV-9956 Dose escalation Dose level 3 Experimental Treatment 1 Intervention

INV-9956 Dose escalation Dose level 3 is co-administered with dexamethasone and fludrocortisone acetate

Group VII: Stage 1 INV-9956 Dose escalation Dose level 2 Experimental Treatment 1 Intervention

INV-9956 Dose escalation Dose level 2 is co-administered with dexamethasone and fludrocortisone acetate

Group VIII: Stage 1 INV-9956 Dose escalation Dose level 1 Experimental Treatment 1 Intervention

INV-9956 Dose escalation Dose level 1 is co-administered with dexamethasone and fludrocortisone acetate

Who Is Running the Clinical Trial?

Shenzhen Ionova Life Sciences Co., Ltd.

Lead Sponsor

Trials

2

Recruited

140+

Findings from Research

In a study of prostate cancer patients, high levels of androgen receptor variant 7 (AR-V7) in circulating tumor cells were found to correlate with resistance to the drugs enzalutamide and abiraterone, with 76.92% of patients showing drug resistance linked to AR-V7 overexpression.

AR-V7 upregulation in prostate cancer cells not only increased their proliferation but also indicated a poorer progression-free survival (PFS) for patients, suggesting that AR-V7 could be a potential biomarker for predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of Androgen Receptor Variant 7 (AR-V7) in Circulated Tumor Cells and Correlation with Drug Resistance of Prostate Cancer Cells. Wang, S., Yang, S., Nan, C., et al.[2021]

Enzalutamide demonstrated significant efficacy in managing non-metastatic castration-resistant prostate cancer, with a median prostate-specific antigen-progression-free survival of 35.0 months in a study of 66 Japanese patients.

The treatment showed a high prostate-specific antigen response rate of 88.9%, with most patients experiencing manageable adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment in Japan (Japanese research for patients with non-metastatic castration-resistant prostate cancer-enzalutamide: JCASTRE-zero)-a prospective single-arm interventional study. Sugimoto, M., Kato, T., Tohi, Y., et al.[2022]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

In the PROSPER trial involving 1401 patients with non-metastatic, castration-resistant prostate cancer, enzalutamide significantly improved metastasis-free survival compared to placebo, indicating its efficacy as a treatment option.

Patients receiving enzalutamide experienced longer times to clinically meaningful pain progression and symptom worsening, while maintaining a high quality of life, suggesting that enzalutamide not only prolongs survival but also enhances overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. Tombal, B., Saad, F., Penson, D., et al.[2021]

In a study of 265 metastatic prostate cancer patients treated with docetaxel, castration status did not influence the risk of severe neutropenia or febrile neutropenia, indicating that other factors may be more critical in assessing patient risk.

The analysis identified that older age (≥75 years) and lack of primary prophylaxis against neutropenia significantly increased the risk of severe neutropenia, while a poor performance status was linked to a higher likelihood of febrile neutropenia, which can inform treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does castration status affect docetaxel-related adverse events? :Identification of risk factors for docetaxel-related adverse events in metastatic prostate cancer. Yanagisawa, T., Kimura, T., Hata, K., et al.[2022]

In a study of 16 patients with castration-resistant prostate tumors, 50% showed a partial response to insulin-potentiation therapy (IPT) combined with low-dose chemotherapy, indicating potential efficacy in this difficult-to-treat population.

No significant side effects were reported during the treatment, suggesting that IPT combined with hormone therapy may be a safe option for patients with advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose chemotherapy with insulin (insulin potentiation therapy) in combination with hormone therapy for treatment of castration-resistant prostate cancer. Damyanov, C., Gerasimova, D., Maslev, I., et al.[2021]

In the PROSPER study involving men with non-metastatic castration-resistant prostate cancer (nmCRPC), treatment with enzalutamide alongside androgen deprivation therapy (ADT) significantly improved survival compared to placebo and ADT.

A notable decline in prostate-specific antigen (PSA) levels after enzalutamide treatment was associated with longer survival and a delay in cancer progression, suggesting that PSA changes can help guide patient monitoring and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary: Can declines in prostate-specific antigen level indicate how long patients with advanced prostate cancer will live when treated with enzalutamide? Hussain, M., Sternberg, CN., Efstathiou, E., et al.[2023]

Castration remains a primary treatment for advanced prostate cancer, achieving an initial response rate of over 60-70%, but the effectiveness typically lasts less than 3 to 5 years due to resistance mechanisms like increased adrenal androgens or mutated androgen receptors.

Newer treatments like abiraterone and enzalutamide show promise as effective second-line therapies for castration-resistant prostate cancer and may also be beneficial as initial treatments, but their use as standard care requires validation through randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line use of novel hormonal agents in prostate cancer: a critical appraisal. Raghavan, D.[2018]

In a Phase II trial involving 16 patients with metastatic prostate cancer, ImuVert was administered weekly for 10 weeks, but no patients showed a response to the treatment, indicating its ineffectiveness for this condition.

The treatment was generally well-tolerated, with only mild, transient flu-like symptoms and localized injection site reactions reported, suggesting a favorable safety profile despite lack of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a new biological response modifier (ImuVert) in advanced prostate cancer. Osborne, CK., Craig, JB., Klein, K., et al.[2019]

In a study of 38 patients with non-metastatic castration sensitive prostate cancer, three months of enzalutamide treatment led to a remarkable 99% decline in prostate-specific antigen (PSA) levels, demonstrating its efficacy without the need for androgen deprivation therapy (ADT).

Enzalutamide treatment was associated with beneficial immune changes, including an increase in natural killer cells and naïve T cells, suggesting potential for future combination therapies in immunotherapy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer. Madan, RA., Karzai, F., Donahue, RN., et al.[2021]

References

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

Expression of Androgen Receptor Variant 7 (AR-V7) in Circulated Tumor Cells and Correlation with Drug Resistance of Prostate Cancer Cells. [2021]

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

Enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment in Japan (Japanese research for patients with non-metastatic castration-resistant prostate cancer-enzalutamide: JCASTRE-zero)-a prospective single-arm interventional study. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. [2021]

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

Does castration status affect docetaxel-related adverse events? :Identification of risk factors for docetaxel-related adverse events in metastatic prostate cancer. [2022]

6. Egypt pubmed.ncbi.nlm.nih.gov

Low-dose chemotherapy with insulin (insulin potentiation therapy) in combination with hormone therapy for treatment of castration-resistant prostate cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Plain language summary: Can declines in prostate-specific antigen level indicate how long patients with advanced prostate cancer will live when treated with enzalutamide? [2023]

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

First-line use of novel hormonal agents in prostate cancer: a critical appraisal. [2018]

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

Phase II trial of a new biological response modifier (ImuVert) in advanced prostate cancer. [2019]

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

Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer. [2021]