BDC-3042 + Pembrolizumab for Advanced Cancers

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

147 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A first-in-human study using BDC-3042 as a single agent and in combination with cemiplimab in patients with advanced malignancies

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.

What safety data exists for BDC-3042 + Pembrolizumab treatment?

Pembrolizumab (Keytruda) has been associated with several immune-related adverse events (irAEs). These include type 1 diabetes mellitus, which occurs in 0.2% of cases, and pneumonitis, which occurs in 1%-5% of patients. Other common adverse reactions include fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions also include colitis, hepatitis, hypophysitis, and thyroid disorders. The safety profile of pembrolizumab has been evaluated in various clinical trials, including those for non-small cell lung cancer and metastatic melanoma. ^{1 2 3 4 5}

What safety information is available for the treatment BDC-3042 + Pembrolizumab?

Pembrolizumab (also known as Keytruda) has been associated with some side effects, including a rare risk of developing type 1 diabetes (a condition where the body cannot produce insulin) in 0.2% of cases and pneumonitis (inflammation of the lungs) in 1%-5% of patients. Common side effects include fatigue, cough, nausea, itching, rash, decreased appetite, constipation, joint pain, and diarrhea. ^{1 2 3 4 5}

Is the drug BDC-3042 combined with Pembrolizumab a promising treatment for advanced cancers?

Yes, the drug combination of BDC-3042 and Pembrolizumab is promising for advanced cancers. Pembrolizumab, also known as Keytruda, has shown success in treating various cancers, including lung cancer and melanoma, by helping the immune system fight cancer cells. It has been approved for several cancer types and has demonstrated significant improvements in patient survival rates. ^{1 4 6 7 8}

What makes the drug BDC-3042 + Pembrolizumab unique for treating advanced cancers?

The combination of BDC-3042 with Pembrolizumab is unique because it pairs a novel agent, BDC-3042, with Pembrolizumab, a well-established PD-1 inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the immune response against advanced cancers, potentially offering a new treatment option where standard therapies may not exist. ^{1 4 6 7 8}

What data supports the idea that BDC-3042 + Pembrolizumab for Advanced Cancers is an effective drug?

The available research shows that Pembrolizumab, a part of the BDC-3042 + Pembrolizumab combination, has been effective in treating various advanced cancers. For example, it has been approved for treating advanced non-small cell lung cancer, endometrial carcinoma, and esophageal or gastroesophageal cancer. These approvals suggest that Pembrolizumab can help improve outcomes for patients with these types of cancers, indicating its potential effectiveness when combined with BDC-3042 for advanced cancers. ^{1 4 7 9 10}

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancers?

Pembrolizumab has shown effectiveness in treating various advanced cancers, including non-small cell lung cancer and melanoma, by improving survival rates compared to chemotherapy. It works by helping the immune system attack cancer cells more effectively. ^{1 4 6 9 10}

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

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, 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 (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]

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]

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]

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 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) 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 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. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

New Approved Use for Keytruda. [2022]

4. China 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. [2022]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]