OBI-992 for Advanced Solid Tumors

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, OBI-992 (also known as BSI-992), to evaluate its effectiveness and safety for individuals with advanced solid tumors, such as certain lung or gastric cancers. The first part of the trial aims to determine the optimal dose, while the second part assesses the treatment's effectiveness in specific cancers. Individuals who have tried other unsuccessful treatments or cannot be cured with local treatments might be suitable candidates. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this new therapy.

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.

Is there any evidence suggesting that OBI-992 is likely to be safe for humans?

Research has shown that OBI-992, a new drug under study, is currently undergoing safety testing in humans. In earlier lab studies, OBI-992 demonstrated potential in fighting cancer. These studies typically serve as the first step to assess a treatment's safety for people.

This is a Phase 1/2 trial, meaning researchers are beginning to test OBI-992 in humans to learn about its safety and determine the best dose. Phase 1 trials focus on safety and identifying a safe dose, while Phase 2 trials examine how well the treatment works against the disease. OBI-992's presence in this phase indicates it has passed initial safety tests in the lab, and researchers are hopeful about its safety in humans.

However, as this is an early trial, detailed safety information for humans might not yet be available. Participants in the trial will help gather this crucial information. It's important to remember that new treatments can carry unknown risks, but participating in the trial aids researchers in understanding and improving the treatment for future patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

OBI-992 is unique because it targets specific receptors on cancer cells, potentially leading to more effective treatment for advanced solid tumors like non-small cell lung cancer, gastric cancer, and small cell lung cancer. Unlike the standard chemotherapy treatments, which attack rapidly dividing cells indiscriminately, OBI-992 is designed to home in on cancer cells, potentially reducing side effects and improving outcomes. This treatment uses a novel active ingredient that may offer a new mechanism of action, giving researchers hope for better precision in attacking tumors without harming healthy cells.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research shows that OBI-992, a treatment targeting the protein TROP2, has promising effects against tumors. In lab studies using cancer cells and patient tumor models, OBI-992 slowed or stopped tumor growth. TROP2, often found in high amounts in many cancer cells, serves as a good target for treatment. By focusing on this protein, OBI-992 aims to deliver cancer drugs directly to the tumor, reducing harm to healthy cells. This trial will explore various treatment arms, including different dosages and cancer indications, to evaluate the effectiveness of OBI-992 for patients with advanced solid tumors, such as lung and stomach cancers. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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

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

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06480240

NCT06480240 | A Phase 1/2 Study of OBI-992 in Subjects ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11791482/

OBI-992, a Novel TROP2-Targeted Antibody–Drug ... In this study, we evaluated the antitumor activity of OBI-992 in cancer cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) models of various ...

3. synapse.patsnap.com synapse.patsnap.com/article/obi-pharma-starts-phase-12-study-of-obi-992-for-cancer-therapy

OBI Pharma Starts Phase 1/2 Study of OBI-992 for Cancer ... This trial marks an important step in evaluating the safety and efficacy of OBI-992 in patients with advanced solid tumors, including non-small ...

4. biospace.com biospace.com/obi-pharma-announces-phase-1-2-study-initiation-for-obi-992-a-trop2-targeted-antibody-drug-conjugate-adc-for-cancer-therapyclinical-trial-to-evaluate-the-safety-and-efficacy-of-obi-992-in-advanced-solid-tumors

OBI Pharma Announces Phase 1/2 Study Initiation for OBI ... OBI plans to enroll patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) ...

5. obipharma.com obipharma.com/news/obi-pharma-announces-phase-1-2-study-initiation-for-obi-992-a-trop2-targeted-antibody-drug-conjugate-adc-for-cancer-therapy/

OBI Pharma announces Phase 1/2 study initiation for OBI-992 ... OBI plans to enroll patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), gastric cancer (GC), and ...

6. obipharma.com obipharma.com/news/obi-pharma-announces-u-s-fda-clearance-of-ind-application-for-a-phase-1-2-study-of-obi-992/

OBI Pharma Announces U.S. FDA Clearance of IND ... First clinical trial to evaluate the safety and efficacy of OBI-992, a novel antibody – drug conjugate (ADC) targeting TROP2.

7. aacrjournals.org aacrjournals.org/mct/article/24/2/163/751277/OBI-992-a-Novel-TROP2-Targeted-Antibody-Drug

OBI-992, a Novel TROP2-Targeted Antibody–Drug Conjugate ... In this study, we evaluated the antitumor activity of OBI-992 in cancer cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) ...

8. delta.larvol.com delta.larvol.com/Products/?ProductId=58b9a7ae-b70f-42d5-a7fa-395f5dee4e87

OBI-992 / OBI Pharma, Biosion Preclinical pharmacokinetic, pharmacodynamic, and safety profile of OBI-992: a novel TROP2-targeted antibody-drug conjugate. (PubMed, Mol Cancer Ther) ...