BA3182 for Cancer

Recruiting at 4 trial locations

Overseen By Ji Hwan Lee

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BioAtla, Inc.

Disqualifiers: Cardiac disease, CNS metastasis, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

168 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug BA3182 for cancer?

The research suggests that drugs similar to BA3182, like PARP inhibitors, can be effective in treating certain types of breast cancer, especially in patients with specific genetic mutations like BRCA. These drugs work by preventing cancer cells from repairing their DNA, which can lead to their death. ^{1 2 3 4 5}

What makes the drug BA3182 unique for cancer treatment?

BA3182 is unique because it targets B-cell receptor-associated protein 31 (BAP31), which is involved in cancer cell proliferation and metastasis. This approach is novel as BAP31 is a cancer/testis antigen, making it a promising target for treating various cancers by potentially inhibiting tumor growth and spread. ^{6 7 8 9 10}

What is the purpose of this trial?

The objective of this study is to assess safety and efficacy of BA3182 in Advanced Adenocarcinoma

Eligibility Criteria

This trial is for adults over 18 with advanced adenocarcinoma that can't be removed by surgery or has spread. Participants must have confirmed diagnosis, good kidney and liver function, stable blood counts, and be able to carry out daily activities with minimal symptoms (ECOG status of 0 or 1).

Inclusion Criteria

My cancer is advanced and cannot be removed by surgery.

My liver is working well.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BA3182 to evaluate safety, tolerability, PK, immunogenicity, and antitumor activity

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BA3182

Trial Overview The study is testing the safety and effectiveness of a new medication called BA3182 in patients who have advanced stages of adenocarcinoma.

Participant Groups

Group I: BA3182 Experimental Treatment 1 Intervention

All Patients will receive BA3182

Who Is Running the Clinical Trial?

BioAtla, Inc.

Lead Sponsor

Trials

7

Recruited

1,500+

Findings from Research

ABT-888, a PARP inhibitor, demonstrated a significant reduction of over 95% in intratumor PAR levels after a single dose in a first-in-human clinical trial, indicating its strong efficacy in targeting cancer cells.

The study established effective methodologies for evaluating drug effects in human tumor models, which could guide future clinical trials for targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical modeling of a phase 0 clinical trial: qualification of a pharmacodynamic assay of poly (ADP-ribose) polymerase in tumor biopsies of mouse xenografts. Kinders, RJ., Hollingshead, M., Khin, S., et al.[2019]

Low expression of the CtIP protein in breast cancer patients is linked to poorer survival rates, indicating its potential role as a prognostic biomarker.

Depleting CtIP in breast cancer cells enhances their sensitivity to PARP inhibitors, suggesting that patients with low CtIP levels may benefit from PARP inhibitor therapies, providing new treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loss of CtIP disturbs homologous recombination repair and sensitizes breast cancer cells to PARP inhibitors. Wang, J., Ding, Q., Fujimori, H., et al.[2020]

BRCA1- or BRCA2-defective tumors are particularly sensitive to PARP-1 inhibitors, which target alternative DNA repair pathways, but challenges such as acquired resistance and the need for predictive biomarkers remain.

The study identified that defects in the Mre11-Rad50-Nbs1 (MRN) complex can sensitize cancer cells to PARP-1 inhibitors, and suggested that monitoring PARsylation and Rad51 foci formation could serve as potential biomarkers for predicting responses to these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment. Oplustilova, L., Wolanin, K., Mistrik, M., et al.[2023]

PARP inhibitors (PARPi) show a weighted mean objective response rate (ORR) of 45% in patients with advanced breast cancer, with significantly higher efficacy (64%) when combined with platinum-based chemotherapy compared to 37% for PARPi alone.

While PARPi treatment improves progression-free survival compared to standard chemotherapy (HR 0.64), it does not significantly affect overall survival (HR 0.87), and there is no difference in response rates between BRCA1 and BRCA2 mutation carriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer. Desnoyers, A., Nadler, M., Wilson, BE., et al.[2023]

The combination of CHK1 and PARP1 inhibitors effectively kills various types of breast cancer cells, including estrogen receptor-positive and triple-negative cells, regardless of certain genetic factors.

In animal models, this combination not only suppressed tumor growth but also improved survival rates, suggesting that using both inhibitors together could be a promising strategy for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly(ADP-ribose) polymerase 1 modulates the lethality of CHK1 inhibitors in mammary tumors. Tang, Y., Hamed, HA., Poklepovic, A., et al.[2021]

BAP31 is upregulated in hepatocellular carcinoma (HCC) and is linked to advanced clinical stages, promoting HCC cell proliferation and tumor growth both in vitro and in vivo.

Targeting BAP31 with an anti-BAP31 antibody significantly inhibited tumor growth in HCC models, suggesting that BAP31 could be a promising therapeutic target for treating this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma. Zhang, X., Jiang, D., Yang, S., et al.[2020]

BAP31 expression is significantly higher in colorectal cancer (CRC) tissues and liver metastatic CRC tissues compared to normal adjacent mucosa, indicating its potential role in cancer progression.

Low levels of BAP31 expression are associated with poorer overall survival and disease-free survival in CRC patients, suggesting that BAP31 could serve as an independent prognostic marker for patient outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low expression of B-Cell-Associated protein 31 is associated with unfavorable prognosis in human colorectal cancer. Ma, C., Jin, RM., Chen, KJ., et al.[2018]

BAP31 promotes colorectal cancer (CRC) angiogenesis by influencing the tumor microenvironment, specifically through exosomes that transform normal fibroblasts into proangiogenic cancer-associated fibroblasts (CAFs).

The study identified that the microRNA miR-181a-5p, regulated by BAP31, targets the RECK protein, leading to increased levels of matrix metalloproteinase-9 (MMP-9) and activation of Smad2/3, which are crucial for fibroblast transformation and angiogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation. Zhang, Q., Wang, C., Li, R., et al.[2023]

The SADA method identified BAP31 as a novel cancer/testis antigen (CTA) that is significantly upregulated in cervical cancer, particularly in stages I, II, and III, and is associated with poor clinical outcomes.

BAP31 promotes cervical cancer cell proliferation and metastasis by regulating the cell cycle and affecting cytoskeletal dynamics, suggesting that targeting BAP31 could be a potential therapeutic strategy to inhibit cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BAP31, a newly defined cancer/testis antigen, regulates proliferation, migration, and invasion to promote cervical cancer progression. Dang, E., Yang, S., Song, C., et al.[2021]

B-cell associated protein 31 (BAP31) levels were found to be significantly higher in hepatocellular carcinoma (HCC) tissues compared to non-cancerous tissues, indicating its potential role in cancer progression.

In a study involving 234 patients in a training cohort and 63 in a validation cohort, lower levels of BAP31 expression were correlated with poorer overall survival, establishing it as an independent prognostic factor for HCC outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low expression of B-cell-associated protein 31 in human primary hepatocellular carcinoma correlates with poor prognosis. Tan, N., Liu, Q., Liu, X., et al.[2022]

References

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

Preclinical modeling of a phase 0 clinical trial: qualification of a pharmacodynamic assay of poly (ADP-ribose) polymerase in tumor biopsies of mouse xenografts. [2019]

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

Loss of CtIP disturbs homologous recombination repair and sensitizes breast cancer cells to PARP inhibitors. [2020]

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

Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment. [2023]

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

Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer. [2023]

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

Poly(ADP-ribose) polymerase 1 modulates the lethality of CHK1 inhibitors in mammary tumors. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Low expression of B-Cell-Associated protein 31 is associated with unfavorable prognosis in human colorectal cancer. [2018]

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

The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation. [2023]

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

BAP31, a newly defined cancer/testis antigen, regulates proliferation, migration, and invasion to promote cervical cancer progression. [2021]

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

Low expression of B-cell-associated protein 31 in human primary hepatocellular carcinoma correlates with poor prognosis. [2022]