BGB-24714 + Combination Therapies for Solid Tumors

Recruiting at 41 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: BeiGene

Must not be taking: Corticosteroids, Immunosuppressants, SMAC mimetics, IAP antagonists

Disqualifiers: Brain metastasis, Recent malignancy, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called BGB-24714, alone or with other treatments, for people with advanced solid tumors. The goal is to find the highest safe dose to use in future studies.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you must have stopped them at least 14 days before starting the trial.

What data supports the effectiveness of the drug BGB-24714 in combination with other therapies for solid tumors?

While there is no direct data on BGB-24714, research shows that combining different cancer treatments, like immunotherapy and targeted therapies, can enhance their effectiveness. For example, combining bevacizumab with chemotherapy has shown improved survival in lung cancer patients, suggesting that similar combination strategies might be beneficial for other solid tumors. ^{1 2 3 4 5}

Is BGB-24714 and its combination therapies safe for humans?

The safety of BGB-24714 specifically is not directly addressed in the provided research articles. However, combination therapies in cancer treatment often have different safety profiles, and some studies indicate that combination therapies can have serious adverse events. It's important to consult with healthcare professionals for detailed safety information specific to BGB-24714. ^{6 7 8 9 10}

What makes the drug BGB-24714 unique for treating solid tumors?

BGB-24714 is unique because it is being studied in combination with other therapies to enhance the immune system's ability to fight solid tumors, potentially offering improved clinical responses and reduced side effects compared to traditional treatments. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for adults with advanced solid tumors that have grown or spread despite standard treatments, or when no treatment options are available. Participants must be in relatively good health and physical condition (ECOG ≤1), able to provide a tumor tissue sample, and not have had certain other cancers or major surgeries recently. They also can't be on steroids or similar meds within 14 days of starting the study.

Inclusion Criteria

My organs are functioning well.

My advanced cancer cannot be surgically removed and I've either tried standard treatments without success or can't tolerate them.

Patient must sign a written informed consent form (ICF); and agree to comply with study requirement.

Exclusion Criteria

I have not had major surgery within the last 28 days.

I have not had a serious infection needing treatment in the last 2 weeks.

I do not have active brain metastasis or untreated brain cancer spread.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of BGB-24714 as monotherapy or in combination with chemoradiation or paclitaxel

6 months

Dose Expansion

BGB-24714 is administered in combination with paclitaxel or docetaxel in participants with selected solid tumors

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BGB-24714 (Epigenetic Modulator)
• Paclitaxel (Taxane)

Trial Overview The trial is testing BGB-24714's safety and tolerability as a standalone treatment and alongside chemotherapy drugs like Carboplatin and Paclitaxel, as well as radiation therapy. It aims to find the highest dose patients can take without severe side effects for future studies.

Participant Groups

Group I: Phase 1b: Dose Expansion Experimental Treatment 4 Interventions

BGB 24714 will be administered in combination with paclitaxel or docetaxel in participants with selected solid tumors.

Group II: Phase 1a: Dose Escalation Part E Experimental Treatment 3 Interventions

Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation in Chinese participants

Group III: Phase 1a: Dose Escalation Part D Experimental Treatment 3 Interventions

Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation

Group IV: Phase 1a: Dose Escalation Part C Experimental Treatment 3 Interventions

Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation

Group V: Phase 1a: Dose Escalation Part B Experimental Treatment 2 Interventions

Participants will receive increasing dose levels of BGB-24714 in combination with paclitaxel

Group VI: Phase 1a: Dose Escalation Part A-CN Experimental Treatment 1 Intervention

Participants will receive escalating doses of BGB-24714 as monotherapy in Chinese participants

Group VII: Phase 1a: Dose Escalation Part A Experimental Treatment 1 Intervention

Participants will receive escalating doses of BGB-24714 as monotherapy

BGB-24714 is already approved in China for the following indications:

Approved in China as BGB-24714 for:

• Esophageal Carcinoma
• Lung Cancer

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

In a study involving 122 patients with advanced solid tumors, the combination of ibrutinib and durvalumab showed an acceptable safety profile, with adverse events consistent with known effects of both drugs.

However, the antitumor activity was limited, with overall response rates of only 2% for pancreatic cancer, 3% for breast cancer, and 0% for non-small cell lung cancer, indicating that this combination may not be effective for these types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors. Hong, D., Rasco, D., Veeder, M., et al.[2021]

In a phase II trial involving 120 patients with non-small-cell lung cancer, combining bevacizumab with erlotinib or chemotherapy showed a favorable safety profile, with fewer patients discontinuing treatment due to adverse events compared to chemotherapy alone.

The combination therapies resulted in improved one-year survival rates (57.4% for bevacizumab-erlotinib and 53.8% for bevacizumab-chemotherapy) compared to 33.1% for chemotherapy alone, suggesting enhanced efficacy in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer. Herbst, RS., O'Neill, VJ., Fehrenbacher, L., et al.[2022]

Immunotherapy has been proven effective for treating various cancers, showing great promise for combining different immunotherapy agents and integrating them with traditional cancer treatments.

Clinical trials that combine CTLA4 and PD1 blockade are setting a standard for future immuno-oncology combination therapies, although there are challenges in customizing these strategies for optimal patient benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving synergistic combinations of targeted immunotherapies to combat cancer. Melero, I., Berman, DM., Aznar, MA., et al.[2022]

Combining immune checkpoint inhibitors (ICIs) with signal transduction inhibitors, like antiangiogenic therapies, has shown enhanced antitumor activity in various solid tumors, leading to regulatory approvals for treatments in cancers such as endometrial and kidney cancer.

Despite these advancements, many patients still experience disease progression after combination treatments, highlighting the need for new strategies to overcome resistance to immunotherapy, which has prompted the development of consensus definitions for resistance to multiagent ICI combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies. Atkins, MB., Ascierto, PA., Feltquate, D., et al.[2023]

In a retrospective analysis of 217 patients from the ECOG 4599 study, those who received bevacizumab (BV) maintenance therapy after induction treatment showed significantly longer progression-free survival (4.4 months) compared to those who received carboplatin and paclitaxel (CP) alone (2.8 months).

The safety profile of BV maintenance was favorable, with less than 1% of patients experiencing severe hematological toxicities and no severe nausea, vomiting, or diarrhea, indicating that BV can be a safe option for maintaining treatment benefits in non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. Lopez-Chavez, A., Young, T., Fages, S., et al.[2015]

A large-scale retrospective study of 2094 cases from the FDA adverse event reporting system found that combining immune checkpoint inhibitors with bevacizumab significantly increases the risk of adverse drug reactions (ADRs) in cancer patients, particularly interstitial lung disease, hypertension, and gastrointestinal bleeding.

The study highlights that combination therapy is an independent risk factor for these ADRs, suggesting the need for careful monitoring and individualized management strategies for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. Gu, T., Jiang, A., Zhou, C., et al.[2023]

Blocking the PD-1 pathway with specific drugs has shown clinical effectiveness in treating advanced cancers like melanoma and lung cancer, by enhancing the body's anti-tumor immune response.

These PD-1/PD-L1 blocking drugs have a manageable safety profile, making them suitable for outpatient treatment and potential use in combination therapies, with ongoing research focused on identifying biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Lipson, EJ., Forde, PM., Hammers, HJ., et al.[2022]

A comprehensive analysis of 329 clinical trials in non-small cell lung cancer revealed distinct safety profiles for combination therapies compared to monotherapies, highlighting that while liver enzyme elevations (AST/ALT) were less common in combination treatments, the risk of bleeding was significantly higher.

The newly developed SAEgnal framework allows for predictive analytics of serious adverse events (SAEs), which could enhance the safety and efficacy of combination therapies in oncology, potentially accelerating drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAEgnal: A Predictive Assessment Framework for Optimizing Safety Profiles in Immuno-Oncology Combination Trials. Prokop, A., Zhang, Y., Mukhopadhyay, P., et al.[2021]

In a phase I trial, BGB-283 was shown to be safe and well-tolerated in patients with solid tumors that have mutations in BRAF, KRAS, and NRAS.

The trial demonstrated that BGB-283 is effective in treating these tumors, indicating its potential as a targeted therapy for specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BGB-283 Deemed Effective in Phase I Study. [2018]

Immune checkpoint inhibitors like CTLA-4 and PD-1 have significantly changed the treatment landscape for solid tumors, including melanoma and lung cancer, by enhancing the body's immune response against cancer cells.

Combining checkpoint inhibitors with other therapies (like chemotherapy or cancer vaccines) aims to improve treatment effectiveness while reducing side effects, highlighting the need for reliable biomarkers to identify patients who will benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges. Kyi, C., Postow, MA.[2021]

In a phase I-IIa study involving 90 patients with advanced solid tumors, BMS-690514 was found to have a maximum tolerated dose of 200 mg daily, demonstrating a manageable safety profile with common side effects like diarrhea and rash.

The drug showed antitumor activity in non-small-cell lung cancer (NSCLC) patients, particularly those with EGFR mutations, achieving disease control in 70% of patients with mutations compared to 29% in those with wild-type EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours. Soria, JC., Baselga, J., Hanna, N., et al.[2022]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

In a phase 1 trial involving 12 patients with advanced solid cancers, the combination therapy of GW5074 and sorafenib showed a favorable safety profile, with most adverse effects being mild (grade 1) and only two cases of grade 3 toxicity.

The co-administration therapy resulted in disease control for 66.7% of participants, indicating promising anti-tumor activity, although GW5074's poor absorption suggests that future formulations may be needed to enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors. Kao, CC., Ho, CL., Yang, MH., et al.[2022]

The combination of the oral taxane BMS-275183 and the monoclonal antibody cetuximab showed significant therapeutic synergy in preclinical models, achieving over 2.6 log cell kill in tumor-bearing mice, which is greater than the effects of either treatment alone.

This combination therapy was well-tolerated and resulted in tumor-free status in some mice, suggesting promising efficacy that warrants further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic synergy of oral taxane BMS-275183 and cetuximab versus human tumor xenografts. Rose, WC., Wild, R.[2016]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors. [2021]

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

Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Evolving synergistic combinations of targeted immunotherapies to combat cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies. [2023]

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

Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. [2015]

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

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. [2023]

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

Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022]

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

SAEgnal: A Predictive Assessment Framework for Optimizing Safety Profiles in Immuno-Oncology Combination Trials. [2021]

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

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. [2023]

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

BGB-283 Deemed Effective in Phase I Study. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Phase I-IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours. [2022]

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors. [2022]

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

Therapeutic synergy of oral taxane BMS-275183 and cetuximab versus human tumor xenografts. [2016]