CHK1 Inhibitor for Lung Cancer

(POTENTIATE Trial)

Recruiting at 14 trial locations

Overseen By Angela Pietrofeso

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boundless Bio

Must not be taking: CHK1 inhibitors, EGFR inhibitors, FGFR inhibitors

Disqualifiers: Hematologic malignancies, CNS malignancy, HBV, others

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

Compensation: Varies

Number of Visits: Unknown

127 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BBI-355 (a CHK1 inhibitor) for individuals with advanced solid tumors, specifically lung cancer. The goal is to determine the drug's safety and the appropriate dose, whether used alone or with other treatments like BBI-825. The trial includes different groups: some will receive only BBI-355, while others will receive it with additional drugs. Suitable candidates are those whose cancer has progressed despite all standard treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new drug.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BBI-355 has promising effects against tumors when used alone in early studies. However, combining it with other drugs like erlotinib and futibatinib has proven difficult for some patients to tolerate due to side effects.

Prospective trial participants should know that this is the first time BBI-355 is being tested in humans. While some information exists from lab studies, the full safety profile remains unknown. The trial aims to find the best dose that balances effectiveness with manageable side effects.

Before deciding to participate, discussing the potential risks and benefits with a healthcare provider is advisable. They can help clarify expectations and guide decisions for your health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lung cancer, which often rely on chemotherapy or specific targeted therapies like EGFR and ALK inhibitors, BBI-355 offers a fresh approach. This investigational drug is a CHK1 inhibitor, which means it works by interfering with a protein that cancer cells use to repair their DNA. This unique mechanism can potentially make cancer cells more vulnerable to damage, especially when combined with other inhibitors like RNR, EGFR, or FGFR. Researchers are excited about BBI-355 because it opens up new possibilities for treating lung cancer by potentially overcoming resistance to existing therapies and enhancing the effectiveness of combination treatments.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Earlier research has shown that BBI-355 interferes with how cancer cells repair their damaged DNA, preventing them from repairing themselves, which is crucial for their survival. In this trial, participants may receive BBI-355 alone or with other treatments. When combined with treatments like EGFR inhibitors, BBI-355 demonstrated strong effects against tumors, suggesting potential effectiveness for certain lung cancers. Additionally, using BBI-355 with an RNR inhibitor delayed cancer resistance to treatment, a common issue. These early findings are encouraging, but further studies are needed to confirm its efficacy. ^{1 2 6 7 8}

Who Is on the Research Team?

Robert Doebele, MD, PhD

Principal Investigator

Boundless Bio

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors like lung, stomach, or breast cancer that's worsened after standard treatments. Participants must have evidence of oncogene amplification and measurable disease. They should be in good physical condition (ECOG PS 0 or 1) and have proper organ function. People with primary brain cancers, certain heart conditions, active hepatitis B/C or HIV, a history of severe lung issues, or those who've had specific transplants can't join.

Inclusion Criteria

Availability of FFPE tumor tissue, archival or newly obtained

Other inclusion criteria per study protocol

Measurable disease as defined by RECIST Version 1.1

Exclusion Criteria

I have a history of hepatitis B, hepatitis C, or HIV.

QTcF > 470 msec

Other exclusion criteria per study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Single agent BBI-355 or combination therapy with EGFR or FGFR inhibitors is administered in 28-day cycles to determine the maximum tolerated dose and recommended Phase 2 dose.

28 days per cycle

Dose Expansion

BBI-355 is administered as a single agent in 28-day cycles to further evaluate safety and efficacy.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent adverse events.

30 days following last dose

What Are the Treatments Tested in This Trial?

Interventions

• BBI-355

Trial Overview The study tests BBI-355 as a new treatment targeting ecDNA in tumors. It's an early-phase trial to find the safest dose when given alone or with other therapies. The drug is taken orally and aims to inhibit CHK1—a protein involved in tumor cell growth.

How Is the Trial Designed?

Group I: Single Agent Dose Expansion Experimental Treatment 1 Intervention

Single agent BBI-355, administered orally in 28-day cycles

Group II: Single Agent Dose Escalation Experimental Treatment 1 Intervention

Single agent BBI-355, administered orally in 28-day cycles

Group III: Dose Escalation in Combination with RNR Inhibitor Experimental Treatment 2 Interventions

Combination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.

Group IV: Dose Escalation in Combination with FGFR Inhibitor Experimental Treatment 2 Interventions

Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.

Group V: Dose Escalation in Combination with EGFR Inhibitor Experimental Treatment 2 Interventions

Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.

Who Is Running the Clinical Trial?

Boundless Bio

Lead Sponsor

Trials

2

Recruited

190+

Published Research Related to This Trial

The combination of the Chk1 inhibitor AZD7762 with the chemotherapy drug gemcitabine significantly enhances the effectiveness of treatment against pancreatic cancer cells, particularly when AZD7762 is administered during or after gemcitabine.

The biomarker pS345 Chk1 was consistently elevated in response to the treatment, indicating that DNA damage plays a key role in the mechanism of action for this combination therapy, supporting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of chk1 phosphorylation as a pharmacodynamic biomarker of chk1 inhibition. Parsels, LA., Qian, Y., Tanska, DM., et al.[2022]

The Chk1 inhibitor V158411 enhances the effectiveness of mTOR inhibitors in p53 mutant colon cancer cells, leading to increased cell death and DNA damage, which suggests a promising combination therapy for this cancer type.

Downregulation of DNA repair proteins by mTOR inhibitors increases sensitivity to Chk1 inhibitors, and high levels of DNA-PKcs may serve as a biomarker to identify patients who could benefit from this combined treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mTORC1 and DNA-PKcs as novel molecular determinants of sensitivity to Chk1 inhibition. Massey, AJ., Stephens, P., Rawlinson, R., et al.[2021]

Targeting Chk1 protein kinase with inhibitors can significantly enhance the effectiveness of cancer treatments, especially when combined with Wee1 inhibitors, as shown in various human cancer cell lines including breast and ovarian cancers.

In vivo studies in mice demonstrated that the combination of Chk1 and Wee1 inhibitors led to greater tumor growth inhibition compared to using either inhibitor alone, without causing toxicity, suggesting a promising new treatment strategy for certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined inhibition of Chk1 and Wee1: in vitro synergistic effect translates to tumor growth inhibition in vivo. Carrassa, L., Chilà, R., Lupi, M., et al.[2020]

The study successfully developed reliable 3D-QSAR models for designing potent Chk1 inhibitors, with strong correlation coefficients indicating the models' predictive power based on a series of diazacarbazoles.

Molecular docking studies identified key interactions necessary for Chk1 inhibition, specifically hydrogen bonds with residues Lys38, Glu85, and Cys87, guiding the design of new inhibitors for potential experimental synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of Novel Chemotherapeutic Agents Targeting Checkpoint Kinase 1 Using 3D-QSAR Modeling and Molecular Docking Methods. Balupuri, A., Balasubramanian, PK., Cho, SJ.[2019]

CHK1 inhibitors are promising in cancer treatment as they enhance the effectiveness of DNA-damaging chemotherapy by blocking CHK1's role in cell cycle arrest and DNA repair, allowing cancer cells to be more susceptible to treatment.

These inhibitors are not only being explored as enhancers of existing therapies but also as standalone treatments, targeting CHK1's critical functions in regulating the cell cycle and DNA replication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CHEK again: revisiting the development of CHK1 inhibitors for cancer therapy. McNeely, S., Beckmann, R., Bence Lin, AK.[2016]

A novel CHK1 inhibitor, compound 13, demonstrated strong potency with an IC50 value of 7.73 nM and effectively suppressed the growth of malignant hematological cell lines, particularly MV-4-11 cells with an IC50 of 0.035 μM.

Compound 13 showed good metabolic stability in mouse liver microsomes and moderate oral bioavailability, indicating its potential as an effective and practical anticancer therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, Synthesis, and Biological Evaluation of Orally Bioavailable CHK1 Inhibitors Active against Acute Myeloid Leukemia. Jin, T., Wang, P., Long, X., et al.[2021]

CCT244747 is the first orally bioavailable Chk1 inhibitor that enhances the effectiveness of radiation therapy in bladder and head and neck cancer cell lines, showing promising results in both in vitro and in vivo models.

The mechanism of action involves disrupting the radiation-induced G2 cell cycle arrest, allowing cancer cells to enter mitosis prematurely, which contributes to its radiosensitizing effects and potential clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation. Patel, R., Barker, HE., Kyula, J., et al.[2022]

Chk1 inhibitors can selectively enhance the effectiveness of DNA-damaging cancer treatments by causing p53-deficient cancer cells to undergo mitotic catastrophe and apoptosis, while normal cells remain unaffected due to their G1 phase arrest.

Since about 50% of human cancers lack functional p53, targeting Chk1 presents a promising strategy for developing new cancer therapies that specifically exploit the vulnerabilities of these cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chk1 inhibitors for novel cancer treatment. Tao, ZF., Lin, NH.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS517

Preclinical and phase 1/2 data of the CHK1 inhibitor BBI- ... Conclusions: The first ecDNA directed therapy, BBI-355, demonstrated significant synergistic anti-tumor activity in combination with targeted ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05827614

NCT05827614 | Study of the CHK1 Inhibitor BBI-355, an ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

3. boundlessbio.com boundlessbio.com/wp-content/uploads/2025/05/Boundless-Bio-Corporate-Update-May-27-2025-FINAL.pdf

Unlocking a New Paradigm in Cancer Treatment via ... Module 1 - EGFR amplification*, BBI-355 & EGFR inhibitor erlotinib ... Human PK data of BBI-355 showed 60 mg Q2D is minimum dose required ...

4. aacr.org aacr.org/wp-content/uploads/2025/10/MTCT25_LBCTAbstracts_titlesONLY.pdf

Current as of October 13, 2025 Late-Breaking/Clinical Trial ... CHK1 inhibitor BBI-355 targets unique dependencies of oncogene amplified cancers. Joshua Lange. Boundless Bio, San Diego, CA, United States. LB- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5312475/

Efficacy and safety of erlotinib in the treatment of metastatic ... Erlotinib monotherapy has shown a significant improvement in median survival, quality of life, and related symptoms in an unselected population of patients.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02705-9/fulltext

682P Preclinical and ongoing phase I study data of the ... The first ecDNA directed therapy, BBI-355, demonstrated significant anti-tumor activity as a single agent and in combination with targeted therapies.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3572994/

Observational study on the efficacy and safety of erlotinib in ... To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study.

8. investors.boundlessbio.com investors.boundlessbio.com/news-releases/news-release-details/boundless-bio-presents-preclinical-and-clinical-pharmacodynamic

Directed Therapy, BBI-355, at the American Association for ... BBI-355 is a novel, oral, selective inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial.