OBI-992 for Advanced Solid Tumors

Recruiting at 9 trial locations

Overseen By OBI Pharma, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: OBI Pharma, Inc

Must not be taking: Prohibited medications

Disqualifiers: Organ transplant, CNS metastases, cardiac abnormality, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

117 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a 2-part trial: Part A (Dose Escalation) is designed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of OBI-992 (Anti-TROP2 antibody drug conjugate, anti-TROP2 monoclonal antibody-cleavable peptide linker-exatecan) as monotherapy. Part B (Cohort Expansion) is intended to further characterize the safety and preliminary clinical activity profile of the RP2D of OBI-992 in subjects with advanced solid tumors.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are taking any concurrent prohibited medications, and you must wait at least 3 weeks after your last chemotherapy or radiation treatment before starting the trial.

What makes the drug OBI-992 unique for treating advanced solid tumors?

OBI-992 (BSI-992) is unique because it may target specific molecular pathways that are not addressed by conventional treatments, potentially offering a novel approach for tumors that are resistant to standard therapies. While the exact mechanism of OBI-992 is not detailed, it could involve targeting pathways like PI3K/AKT/mTOR, which are implicated in various cancers, including ovarian clear cell carcinoma. ^{1 2 3 4 5}

Eligibility Criteria

This clinical trial is open to individuals with advanced solid tumors. Participants must meet specific health criteria, which are not detailed here. Those who do not fit the study's requirements or have conditions that could interfere with the trial will be excluded.

Inclusion Criteria

My advanced cancer cannot be cured with surgery or radiation.

I have either tried standard treatments without success, been told they won't work for me, or I've chosen not to receive them.

Measurable disease (i.e., at least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1])

Exclusion Criteria

I have not had TROP2 ADC therapy before joining Phase 2.

I haven't had chemotherapy, radiation, or biologic therapy recently.

Known hypersensitivity to OBI-992 or its excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A of the trial to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of OBI-992 as monotherapy

Up to 2 years and 2 months

Cohort Expansion

Part B of the trial to further characterize the safety and preliminary clinical activity profile of the RP2D of OBI-992 in subjects with advanced solid tumors

Up to 2 years and 2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• OBI-992

Trial Overview The trial is testing OBI-992, a drug designed to target and kill tumor cells. It has two parts: Part A finds the highest dose patients can take without serious side effects (MTD), and Part B tests this dose in more people to see if it's safe and works against cancer.

Participant Groups

Group I: Phase 2 Cohort Expansion - Cohort 3 Experimental Treatment 1 Intervention

Gastric cancer indication cohort - OBI-992 dosed at putative recommended phase 2 dose.

Group II: Phase 2 Cohort Expansion - Cohort 2 Experimental Treatment 1 Intervention

Small cell lung cancer indication cohort - OBI-992 dosed at putative recommended phase 2 dose.

Group III: Phase 2 Cohort Expansion - Cohort 1b Experimental Treatment 1 Intervention

Non-small cell lung cancer indication cohort - Randomized dose optimization cohort. Dose level to be determined by the Safety Review Committee based on data available.

Group IV: Phase 2 Cohort Expansion - Cohort 1a Experimental Treatment 1 Intervention

Non-small cell lung cancer indication cohort - Randomized dose optimization cohort. Dose level to be determined by the Safety Review Committee based on data available.

Group V: Phase 1 Dose Escalation - Cohort 6 Experimental Treatment 1 Intervention

OBI-992 at dose level 10 mg/kg, Q3W

Group VI: Phase 1 Dose Escalation - Cohort 5 Experimental Treatment 1 Intervention

OBI-992 at dose level 8 mg/kg, Q3W

Group VII: Phase 1 Dose Escalation - Cohort 4 Experimental Treatment 1 Intervention

OBI-992 at dose level 6 mg/kg, Q3W

Group VIII: Phase 1 Dose Escalation - Cohort 3 Experimental Treatment 1 Intervention

OBI-992 at dose level 4 mg/kg, Q3W

Group IX: Phase 1 Dose Escalation - Cohort 2 Experimental Treatment 1 Intervention

OBI-992 at dose level 2 mg/kg, Q3W

Group X: Phase 1 Dose Escalation - Cohort 1 Experimental Treatment 1 Intervention

OBI-992 at dose level 1 mg/kg, Q3W

OBI-992 is already approved in United States, China for the following indications:

Approved in United States as OBI-992 for:

• None approved yet; Orphan Drug Designation for gastric cancer

Approved in China as OBI-992 for:

• None approved yet

Who Is Running the Clinical Trial?

OBI Pharma, Inc

Lead Sponsor

Trials

9

Recruited

1,500+

Findings from Research

In a study of 73 clear cell adenocarcinoma of the ovary (OCC) cases, 37% showed amplification of the Met gene, which is linked to poorer survival outcomes in early-stage patients, indicating its role in the tumor's aggressiveness.

Targeting the Met signaling pathway may offer a promising treatment strategy for OCC, as reducing Met expression led to increased cell death and decreased viability in cancer cells with Met amplification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis. Yamashita, Y., Akatsuka, S., Shinjo, K., et al.[2021]

In a study of 124 patients with advanced-stage ovarian clear cell carcinoma (OCCC), researchers identified that 91% of tumors had alterations in key signaling pathways, particularly the PI3K/AKT/mTOR pathway, indicating a potential target for treatment.

The study found that OCCC cell lines and patient-derived xenografts were highly sensitive to mTORC1/2 inhibition using the drug AZD8055, suggesting it could be an effective treatment strategy for this type of cancer, which is typically resistant to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma. Caumanns, JJ., Berns, K., Wisman, GBA., et al.[2022]

Ovarian cancer cells with BRCA1/2 mutations are more responsive to the PARP inhibitor Niraparib, indicating a potential targeted treatment approach for these patients.

The combination of Niraparib and the anti-angiogenic drug Brivanib not only enhances the effectiveness of Niraparib but also promotes multiple forms of programmed cell death in ovarian cancer cells, suggesting a synergistic therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological effects of Niraparib and its combination with angiogenic inhibitor in ovarian cancer. Liu, H., Chen, X., Tang, C., et al.[2023]

A 53-year-old woman with stage IIIc ovarian clear cell carcinoma (OCCC) showed a partial response to a multikinase inhibitor, highlighting the potential for targeted therapies in treating this chemoresistant subtype of ovarian cancer.

Despite having a PIK3CA mutation, the tumor did not respond to PI3K/mTOR pathway inhibitors, indicating the need for better biomarkers to predict which targeted therapies will be effective for OCCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies. Rahman, M., Nakayama, K., Ishibashi, T., et al.[2021]

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]

References

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

Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis. [2021]

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

Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma. [2022]

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

Pharmacological effects of Niraparib and its combination with angiogenic inhibitor in ovarian cancer. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies. [2021]

5. 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]