BDC-3042 + Pembrolizumab for Advanced Cancers

No longer recruiting at 5 trial locations

Overseen By Bolt Biotherapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bolt Biotherapeutics, Inc.

Must not be taking: Corticosteroids, Immunosuppressants, others

Disqualifiers: Cardiac disease, Pulmonary disease, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment, BDC-3042, both alone and with pembrolizumab (an immunotherapy), for individuals with advanced cancers. The focus includes cancers such as melanoma, triple-negative breast cancer, and certain lung and kidney cancers, particularly when they no longer respond to standard treatments. Participants should have cancer that has spread or cannot be surgically removed and must have tried other treatments without success. This trial offers an opportunity for those with limited options in battling their disease. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, certain conditions and treatments, like systemic immunosuppressive therapy or investigational agents, are excluded. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain conditions and treatments, like systemic immunosuppressive therapy or investigational agents, may require adjustments. It's best to discuss your specific medications with the trial team.

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

Research has shown that BDC-3042 was well-tolerated in early tests with patients who have advanced cancers. Patients managed doses up to 10 mg/kg without major problems, suggesting safety at these levels. This is encouraging for those considering joining a trial.

For pembrolizumab, extensive safety information is already available. The FDA has approved it for various cancers, indicating thorough safety checks. Most people handle pembrolizumab well, though some may experience side effects like tiredness or skin reactions.

These findings suggest that both BDC-3042 and pembrolizumab have demonstrated a reasonable level of safety in past studies. However, treatments can affect people differently. Always discuss potential risks with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because BDC-3042 offers a fresh approach by potentially modulating the tumor microenvironment, a strategy not commonly seen in current treatments like chemotherapy or targeted therapies. This unique mechanism might enhance the immune system's ability to recognize and destroy cancer cells. Meanwhile, combining BDC-3042 with pembrolizumab, a well-known immune checkpoint inhibitor, could amplify the immune response, offering hope for better outcomes in advanced cancers.

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

Research shows that BDC-3042 is a new treatment that may help fight advanced cancers. In studies with gradually increased doses, researchers tested BDC-3042 for safety and early signs of effectiveness in patients with serious cancers, such as non-small cell lung cancer. Although the data remains early, this treatment aims to boost the immune system to attack cancer cells. In this trial, some participants will receive BDC-3042 alone, while others will receive a combination of BDC-3042 and cemiplimab. Pembrolizumab, a well-known treatment that helps the immune system find and destroy cancer cells, has been used successfully in many types of cancer, offering hope that these treatments together might be effective. ^{1 3 6 7 8}

Who Is on the Research Team?

Bolt Clinical Development

Principal Investigator

Bolt Biotherapeutics

Are You a Good Fit for This Trial?

Adults with certain advanced cancers (like ovarian, lung, breast, head and neck, renal cell carcinoma or colorectal cancer) that have worsened despite standard treatments. They must be in relatively good health otherwise, not planning to conceive (or will use effective contraception), and have no serious heart issues or other conditions that could interfere with the trial.

Inclusion Criteria

I am using a highly effective birth control method during and 4 weeks after treatment.

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

Your disease can be measured using specific guidelines called Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

Exclusion Criteria

You have had a bad reaction to any part of the BDC-3042 medication or the treatment being studied.

Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study

Patient is a lactating mother or pregnant as confirmed by pregnancy tests within 7 days prior to start of study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of BDC-3042 as a single agent and in combination with cemiplimab to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), or maximum protocol dose (MPD)

Up to 21 days

Expansion

Selected dose administered as monotherapy and in combination with cemiplimab to patients with selected advanced malignancies

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BDC-3042
• Pembrolizumab

Trial Overview The study is testing BDC-3042 alone and combined with Pembrolizumab to see how well they work against various advanced cancers. It's a first-in-human trial meaning it's the first time these drugs are being tested in people for safety and effectiveness.

How Is the Trial Designed?

Group I: Single agent BDC-3042 Experimental Treatment 1 Intervention

Escalating doses followed by expansion targeting advanced malignancies

Group II: Combination BDC-3042 plus cemiplimab Experimental Treatment 2 Interventions

Escalating doses followed by expansion targeting advanced malignancies

Who Is Running the Clinical Trial?

Bolt Biotherapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

330+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT154/761845/Abstract-CT154-BDC-3042-a-first-in-class-Dectin-2

Abstract CT154: BDC-3042, a first-in-class Dectin-2 agonist, in ... BBI-20233042 is a phase 1/2, first-in-human, dose escalation and expansion study of BDC-3042 in patients with advanced cancers.

2. investors.boltbio.com investors.boltbio.com/static-files/7935407c-994d-4c60-9f4b-89d68b4fd049

BDC-3042, a first-in-class Dectin-2 agonist, in patients with ... BDC-3042, a first-in-class Dectin-2 agonist, in patients with advanced malignancies: Results from the first-in-human dose-escalation study. Ecaterina E ...

3. adcreview.com adcreview.com/clinical-trials-update/what-to-expect-at-aacr-2025-bolt-to-present-data-from-phase-1-dose-escalation-study-of-bdc-3042/

What to Expect at AACR 2025: Bolt to Present Data ... Bolt Biotherapeutics will present data from the Phase 1 dose-escalation clinical study of BDC-3042 in patients with advanced cancers.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT06052852

Study of BDC-3042 as Single Agent and in Combination ... This single-agent, dose-escalation Phase 1 clinical study is evaluating BDC-3042 in patients with metastatic or unresectable triple-negative breast cancer (TNBC) ...

5. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/bolt-biotherapeutics-presents-promising-bdc-1042-data-at-aacr-2025/

Bolt Biotherapeutics Presents Promising BDC-1042 Data ... The Phase 1 trial focuses on BDC-3042's efficacy in patients with advanced solid tumors, including non-small cell lung cancer (NSCLC). This data ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2695

A phase 1/2 study of BDC-3042, a novel dectin-2 agonistic ... Methods: This study is enrolling up to 185 patients with advanced cancers, including non-small cell lung cancer, melanoma, triple-negative ...

7. jitc.bmj.com jitc.bmj.com/content/jitc/11/Suppl_1/A815.full.pdf

a phase 1/2 study of bdc-3042, a novel dectin-2 agonistic ... Part 2 is planned to start once single agent BDC-3042 safety data are available. Part 1 will be the dose escalation. The dose-expansion phase of the study will.

8. researchgate.net researchgate.net/publication/375150655_720_A_phase_12_study_of_BDC-3042_a_novel_Dectin-2_agonistic_antibody_in_patients_with_advanced_cancers

720 A phase 1/2 study of BDC-3042, a novel Dectin- ... ... BDC-3042 safety data are available. Part 1 will be the dose escalation. The dose-expansion phase of the study will evaluate preliminary anti- ...