IMP9064 +/- Senaparib for Solid Tumors

Overseen By Xiangna Chen

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Impact Therapeutics, Inc.

Must not be taking: Chemotherapy, Immunotherapy, Hormonal therapy, others

Disqualifiers: CNS tumors, Cardiovascular conditions, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

61 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called IMP9064, which may stop cancer cells from fixing their damaged DNA. It is aimed at patients with advanced solid tumors who need new treatment options. The medicine works by blocking proteins that help cancer cells repair themselves, making it harder for them to survive.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic cancer therapy, including chemotherapy, immunotherapy, and hormonal therapy, at least 28 days before starting the study drug. If you are on low-dose corticosteroids, you may still participate, but continuous treatment with proton pump inhibitors or potassium competitive acid blockers is not allowed.

What data supports the effectiveness of the drug IMP9064 +/- Senaparib for solid tumors?

The research mentions olaparib, a drug similar to senaparib, which has shown effectiveness in treating prostate cancer with specific genetic alterations, and has been studied in combination with other treatments for head and neck cancer. This suggests that similar drugs might be effective in treating certain types of cancer. ^{1 2 3 4 5}

What safety data exists for Senaparib in humans?

Senaparib has been studied in humans for safety in patients with advanced solid tumors, showing it is generally safe and tolerable in early trials. ^{2 6 7 8 9}

What makes the drug IMP9064 +/- Senaparib unique for treating solid tumors?

IMP9064 combined with Senaparib is unique because it involves a novel poly(ADP-ribose) polymerase inhibitor, Senaparib, which has shown strong antitumor activity in early studies. This combination may offer a new approach for treating solid tumors by targeting specific pathways involved in cancer cell repair and survival. ^{6 7 10 11 12}

Eligibility Criteria

Adults with advanced solid tumors who have not responded to standard treatments or for whom no standard treatment exists. They must be able to perform daily activities with minimal assistance (ECOG 0-1), provide tumor tissue samples, and have a life expectancy of at least 12 weeks. Women must be post-menopausal, not pregnant, and willing to use effective contraception; men should either be vasectomized or agree to use contraception.

Inclusion Criteria

I am 18 years old or older.

Provision of tumor tissue samples

My AST cancer doesn't respond to standard treatments or I can't tolerate them.

Exclusion Criteria

I have a serious heart condition.

I cannot swallow pills.

I have not received any live vaccines within the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive IMP9064 monotherapy in a dose-escalation format to determine the Maximum Tolerable Dose

11 months

Dose-expansion

Participants receive IMP9064 monotherapy or in combination with PARP inhibitor Senaparib to evaluate safety and efficacy

11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• IMP9064

Trial Overview The trial is testing IMP9064 alone or combined with Senaparib in patients with advanced solid tumors. It's an open-label study, meaning both the researchers and participants know what treatment is being given. The goal is to assess how safe and effective these treatments are.

Participant Groups

Group I: IMP9064 Monotherapy Experimental Treatment 1 Intervention

Dose-escalation IMP9064 administered orally on empty stomach once/twice daily

Who Is Running the Clinical Trial?

Impact Therapeutics, Inc.

Lead Sponsor

Trials

15

Recruited

1,600+

Findings from Research

In the PROFOUND phase III trial, olaparib demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) for prostate cancer patients with BRCA1/2 mutations.

These benefits were observed across various subgroups of patients, indicating olaparib's efficacy as a targeted treatment for this specific genetic profile in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial. Mateo, J., de Bono, JS., Fizazi, K., et al.[2023]

In a phase II trial involving 41 patients with operable head and neck squamous cell carcinoma (HNSCC), preoperative treatment with olaparib, either alone or in combination with cisplatin or durvalumab, was found to be safe and resulted in a significant reduction in tumor cell proliferation, as indicated by a decrease in Ki67 of at least 25% in 44.8% of treated patients.

The treatment also modulated the tumor microenvironment, leading to increased levels of PD-L1 and changes in macrophage polarization, suggesting that combining olaparib with other therapies may enhance its antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. Moutafi, M., Koliou, GA., Papaxoinis, G., et al.[2023]

In a large registry study involving 1976 patients with metastatic castration-resistant prostate cancer, sipuleucel-T immunotherapy demonstrated a median overall survival of 30.7 months, indicating its potential effectiveness in prolonging life for this patient group.

The treatment was associated with a low incidence of serious adverse events (3.9%) and cerebrovascular events (2.8%), suggesting that sipuleucel-T is a relatively safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. Higano, CS., Armstrong, AJ., Sartor, AO., et al.[2021]

In the Phase III PROfound study, olaparib demonstrated improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to control treatments in Asian patients with metastatic castration-resistant prostate cancer, particularly in those with BRCA gene alterations.

The safety profile of olaparib in the Asian subset was consistent with the global population, showing no new safety concerns, indicating it is a well-tolerated treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Matsubara, N., Nishimura, K., Kawakami, S., et al.[2023]

Niraparib has been approved by the FDA for patients with complete or partial response to first-line platinum-based chemotherapy, regardless of their BRCAm or HRD status, expanding treatment options for more patients.

Olaparib, in combination with bevacizumab, has also received FDA approval for patients with epithelial ovarian cancer, indicating that PARP inhibitors are now beneficial not only for BRCAm and HRD-deficient patients but also for those with HRD-proficient tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PARP inhibitors in the treatment of ovarian cancer: a review. Washington, CR., Moore, KN.[2023]

Senaparib, a selective PARP inhibitor, was well tolerated in a phase 1 study involving 39 patients with advanced solid tumors, with no dose-limiting toxicities observed and most side effects being mild (grade 1-2).

The study showed promising preliminary efficacy, particularly in patients with BRCA mutations, where the overall response rate was 33.3%, while the recommended phase 2 dose was established at 100 mg daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 dose-escalation study of the poly(ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors. Gao, B., Voskoboynik, M., Cooper, A., et al.[2023]

Senaparib, a new drug for treating advanced solid tumors, was found to be well tolerated in a study of 57 patients, with no dose-limiting toxicities reported and a recommended phase II dose identified as 100 mg once daily.

The drug showed promising antitumor activity, with an overall objective response rate of 22.7%, and particularly higher efficacy (26.9%) in patients with BRCA1/BRCA2 mutations, indicating its potential effectiveness in specific genetic contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors: A Phase I Trial. Cao, J., Guo, H., Ji, D., et al.[2023]

Olaparib significantly improves overall survival in patients with recurrent platinum-sensitive ovarian cancer, with a hazard ratio of 1.24 based on a meta-analysis of 7 randomized controlled trials involving 2406 patients.

However, the treatment is associated with a higher incidence of adverse events, particularly for grades 3 or higher, indicating that while olaparib is effective, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. Chen, Q., Li, X., Zhang, Z., et al.[2022]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[2022]

In a phase I study involving 12 patients with advanced solid tumors, the combination of olaparib and bevacizumab was found to be generally well tolerated, with no dose-limiting toxicities reported.

The most common side effects were mild nausea and fatigue, indicating that the treatment has an acceptable safety profile, making it a candidate for further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. Dean, E., Middleton, MR., Pwint, T., et al.[2023]

In a study of 65 patients with advanced serous ovarian cancer in mainland China, olaparib showed a median progression-free survival (PFS) of 4.2 months, with better outcomes for patients with BRCA mutations (5.3 months) compared to those with wild-type BRCA (3.1 months).

Patients receiving olaparib as maintenance therapy had significantly longer PFS (between 9.0 and 10.0 months) compared to those on active therapy (3.1 to 3.0 months), and the treatment was generally well-tolerated, with 87% of patients experiencing low-grade adverse events like fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau. Cao, Y., Chen, H., Huang, Y., et al.[2021]

A reliable reverse phase-high performance liquid chromatography (RP-HPLC) method was developed for accurately estimating olaparib in tablet formulations, demonstrating high precision and linearity over a range of concentrations.

The method effectively separates olaparib from excipients and has been validated according to international guidelines, ensuring its suitability for quality control in pharmaceutical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability Indicating Assay Method for the Quantitative Determination of Olaparib in Bulk and Pharmaceutical Dosage Form. Chaudhary, A., Tonk, R., Dagur, P., et al.[2022]

References

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

Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial. [2023]

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

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. [2023]

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

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. [2021]

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

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

PARP inhibitors in the treatment of ovarian cancer: a review. [2023]

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

A phase 1 dose-escalation study of the poly(ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors. [2023]

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

Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors: A Phase I Trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022]

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

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]

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

Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. [2023]

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

Real-world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau. [2021]

12. Turkey pubmed.ncbi.nlm.nih.gov

Stability Indicating Assay Method for the Quantitative Determination of Olaparib in Bulk and Pharmaceutical Dosage Form. [2022]