OP-3136 for Cancer

Recruiting at4 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Olema Pharmaceuticals, Inc.

Must be taking: Endocrine therapy, CDK4/6 inhibitor

Disqualifiers: CNS metastases, Cardiac disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a first-in-human, open-label, multicenter phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of OP-3136, a lysine acetyltransferases 6A and 6B (KAT6A/B) inhibitor, in participants with advanced solid tumors. This study consists of 2 parts: a dose escalation part (Part 1) and dose expansion part (Part 2).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants must have received certain prior therapies, which suggests that some medications might be continued. It's best to discuss your specific medications with the trial team.

How is the drug OP-3136 different from other cancer treatments?

OP-3136 is unique because it targets the STAT3 pathway, which is involved in cancer cell growth and survival. This drug is similar to OPB-31121, a STAT3 inhibitor that has shown promise in reducing tumor growth by disrupting the JAK2/STAT3 signaling pathway, making it potentially effective for cancers that rely on this pathway. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for individuals with advanced or metastatic solid tumors, such as breast, lung, prostate, and non-small cell lung cancer. Participants should have a tumor that has progressed after treatment or be untreatable with standard therapies.

Inclusion Criteria

I have had up to 4 treatments for prostate cancer, including hormone therapy.

My cancer is advanced or metastatic and fits the specific type required.

My cancer cannot be surgically removed, has spread, and no effective treatments are left.

Exclusion Criteria

I have been treated with a KAT6A/B inhibitor before.

My advanced cancer has spread to vital organs and poses an immediate risk to my life.

I have had heart problems or significant heart disease in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluation of safety, tolerability, and PK in a range of doses of OP-3136 to determine the maximum tolerated dose and recommended dose/regimen for expansion

8-12 weeks

Dose Expansion

Evaluation of the recommended dose and regimen from Part 1 in expansion cohorts of participants with ER+ HER2- mBC and mCRPC

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• OP-3136 (Lysine Acetyltransferases Inhibitor)

Trial Overview The study tests OP-3136, an experimental drug targeting specific enzymes (KAT6A/B) in cancer cells. It's conducted in two parts: first to find the right dose (Part 1), then to see how well it works at that dose (Part 2).

Participant Groups

Group I: Part 2 Dose Expansion - mCRPC Experimental Treatment 1 Intervention

Group II: Part 2 Dose Expansion - mBC Experimental Treatment 1 Intervention

Group III: Part 1 Dose Escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Olema Pharmaceuticals, Inc.

Lead Sponsor

Trials

5

Recruited

970+

Findings from Research

The phase I study of OPB-31121, an oral STAT3 inhibitor, involved 25 patients with advanced solid tumors and established a maximum-tolerated dose (MTD) of 800 mg/day, demonstrating that the drug is safe and relatively well tolerated.

Preliminary results indicated some antitumor activity, with two patients experiencing tumor shrinkage and eight patients maintaining stable disease, suggesting potential efficacy in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors. Oh, DY., Lee, SH., Han, SW., et al.[2022]

The study of OPB-51602, a STAT3 inhibitor, involved 51 patients and established a maximum-tolerated dose (MTD) of 5 mg, with a recommended phase II dose of 4 mg due to tolerability at lower doses.

OPB-51602 showed promising antitumor activity, particularly in patients with non-small-cell lung cancer (NSCLC), with two patients achieving partial responses, highlighting its potential effectiveness in treating refractory solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies. Wong, AL., Soo, RA., Tan, DS., et al.[2022]

OPB-31121, a novel STAT3 inhibitor, effectively downregulated key proteins in the JAK/STAT signaling pathway, leading to reduced cell proliferation and increased apoptosis in gastric cancer cells.

In preclinical models, OPB-31121 demonstrated synergistic effects when combined with standard chemotherapy drugs like 5-fluorouracil and cisplatin, suggesting its potential as a promising treatment option for gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. Kim, MJ., Nam, HJ., Kim, HP., et al.[2022]

The study established that the recommended phase II dose of intraperitoneal (IP) paclitaxel for treating gastric cancer with peritoneal metastasis is 60 mg/m2, as it was well-tolerated with manageable adverse events in 13 patients.

The combination of IP paclitaxel and intravenous FOLFOX showed promising results, with a median overall survival of 16.6 months and a conversion surgery rate of 23.1%, indicating potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intraperitoneal Paclitaxel Plus Intravenous Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) for Gastric Cancer with Peritoneal Metastasis. Kang, SH., Min, SH., Kim, JW., et al.[2022]

In a phase 1 trial involving 24 patients with advanced hepatocellular carcinoma (HCC), OPB-31121, a STAT3 inhibitor, showed limited antitumor activity, with only 25-42.9% of patients achieving stable disease for 8 weeks or more.

The treatment was associated with significant side effects, including nausea, vomiting, and peripheral neuropathy, which raised concerns about the feasibility of long-term use, leading to the conclusion that further development of OPB-31121 for HCC is challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 and pharmacological trial of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma. Okusaka, T., Ueno, H., Ikeda, M., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors. [2022]

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

Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. [2022]

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

Safety and Efficacy of Intraperitoneal Paclitaxel Plus Intravenous Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) for Gastric Cancer with Peritoneal Metastasis. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Phase 1 and pharmacological trial of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma. [2022]