HMBD-002 + Pembrolizumab for Cancer

Recruiting at 6 trial locations

Overseen By Kon Yew Kwek, BMBCh, DPhil

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hummingbird Bioscience, Inc.

Must not be taking: VISTA agents, Immunosuppressants

Disqualifiers: Autoimmune, Cardiovascular, Pulmonary, HIV, others

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

Compensation: Varies

Number of Visits: 7

313 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1/2, open-label, multi-center, first-in-human, two-stage (Part 1: dose escalation and Part 2: dose expansion) study evaluating multiple doses and schedules of intravenously (IV) administered HMBD-002, with or without pembrolizumab KEYTRUDA®, in patients with advanced solid tumors (i.e., locally advanced and unresectable, or metastatic).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on systemic corticosteroids or immunosuppressive therapy, you may need to adjust your dosage as the trial excludes those on doses exceeding 10 mg daily of prednisone equivalent.

What data supports the effectiveness of the drug pembrolizumab in cancer treatment?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, has been effective in treating various types of cancer, including non-small cell lung cancer and melanoma. It has improved survival rates and response to treatment in these cancers. ^{1 2 3 4 5}

Is the combination of HMBD-002 and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA) has been studied in various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as lung inflammation and thyroid problems. Safety data specific to HMBD-002 is not provided, so it's important to discuss potential risks with your doctor. ^{1 3 6 7 8}

What makes the drug combination of HMBD-002 and Pembrolizumab unique for cancer treatment?

This treatment is unique because it combines HMBD-002 with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells by blocking a pathway that tumors use to hide from immune cells. Pembrolizumab has shown effectiveness in various cancers, and combining it with HMBD-002 may enhance its ability to target and destroy cancer cells. ^{1 2 3 4 9}

Eligibility Criteria

Adults with advanced solid tumors, including specific types of breast and lung cancer without available beneficial therapies. Participants must have measurable disease, be at least 18 years old with good performance status and organ function, agree to contraception, and provide informed consent. Excludes those with certain infections or immune conditions, recent high-dose radiotherapy to the lungs, severe treatment-related adverse events from similar drugs, uncontrolled diseases or other active cancers.

Inclusion Criteria

I agree to follow birth control advice for 4 months after my last treatment.

My blood, kidney, and liver functions are all within normal ranges.

Patient must give informed written consent for the study

Exclusion Criteria

I am HIV positive.

I have a serious lung condition that is not under control.

I had radiotherapy less than 2 weeks ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Phase (Monotherapy)

HMBD-002 administered as a 60-minute IV infusion as a monotherapy on Days 1, 8, and 15 of a 21-day cycle

21 days per cycle

3 visits per cycle (in-person)

Dose Escalation Phase (Combination Therapy)

HMBD-002 administered as a 60-minute IV infusion at escalating doses in combination with pembrolizumab KEYTRUDA®

21 days per cycle

3 visits per cycle (in-person)

Dose Expansion Phase (Combination Therapy)

HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion in combination with pembrolizumab KEYTRUDA®

21 days per cycle

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days post last dose

Treatment Details

Interventions

• HMBD-002
• Pembrolizumab

Trial Overview The trial is testing HMBD-002 alone or combined with Pembrolizumab in patients with various advanced solid tumors. It's a two-part study: first finding the right dose (dose escalation) then expanding that dose to more patients (dose expansion). The treatments are given intravenously on different schedules.

Participant Groups

Group I: Part 2 - Dose Expansion (Monotherapy) Experimental Treatment 1 Intervention

HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion as a monotherapy in patients with TNBC or NSCLC.

Group II: Part 2 - Dose Expansion (Combination Therapy) Experimental Treatment 2 Interventions

HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion in combination with pembrolizumab KEYTRUDA® at the standard labeled dose in patients with TNBC or NSCLC.

Group III: Part 1 - Dose Escalation Phase (Monotherapy) Experimental Treatment 1 Intervention

HMBD-002 administered as a 60-minute IV infusion as a monotherapy. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle.

Group IV: Part 1 - Dose Escalation Phase (Combination Therapy) Experimental Treatment 2 Interventions

HMBD-002 administered as a 60-minute IV infusion at escalating doses in combination with pembrolizumab KEYTRUDA®. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle. The treatment pembrolizumab KEYTRUDA® will be administered as a 30-minute IV infusion at a dose of 200 mg on Day 1 of every 21-day cycle.

Who Is Running the Clinical Trial?

Hummingbird Bioscience, Inc.

Lead Sponsor

Trials

1

Recruited

310+

Hummingbird Bioscience

Lead Sponsor

Trials

4

Recruited

560+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

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]

The maximum tolerated doses (MTDs) for the combination of pembrolizumab and trametinib were established, with concurrent dosing showing a lower objective response rate (0%) compared to intermittent dosing (27%).

While the combination treatment had manageable safety profiles, with 31% of patients experiencing grade 3/4 treatment-related adverse events in the concurrent group, the overall antitumor activity was limited, suggesting that this combination may not be highly effective for solid tumors and BRAF wild-type melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. Maio, M., Carlino, MS., Joshua, AM., et al.[2022]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

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) 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 (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

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]

References

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. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

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

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

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. [2022]

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

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

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

7. 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]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. [2019]

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

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