HMBD-002 + Pembrolizumab for Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HMBD-002, either alone or with pembrolizumab (an immunotherapy), for individuals with advanced solid tumors. Researchers aim to determine the optimal dose and assess its effectiveness in treating cancers like triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) that have not responded to other treatments. The study seeks participants with advanced or metastatic cancer who have exhausted other treatment options. Participants must be able to undergo tumor biopsies and have no remaining effective therapy options. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

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

Research has shown that HMBD-002 has promising safety results from early studies. In tests with animals such as rats and monkeys, the treatment was well-tolerated, with no serious side effects linked to the drug. This suggests it might be safe for humans as well.

When combined with pembrolizumab (also known as KEYTRUDA®), the combination was also tested. Results indicated it was safe, even at higher doses. Pembrolizumab is already approved for treating various cancers and is generally safe, though it can cause side effects like tiredness and cough.

Overall, early data for both HMBD-002 alone and with pembrolizumab suggest they are well-tolerated. However, as this is an early-phase study, the main goal is to assess safety and determine the right dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of HMBD-002 and pembrolizumab for treating triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) because they bring fresh approaches to tackling these tough cancers. Unlike standard treatments, which often rely on chemotherapy and established immunotherapies, HMBD-002 targets a unique pathway, potentially enhancing the immune system's ability to fight cancer cells. When combined with pembrolizumab, a well-known checkpoint inhibitor, this treatment could offer a one-two punch by not only inhibiting cancer cell growth but also boosting the immune response. This novel combination is promising because it may provide a more effective treatment option with potentially fewer side effects than traditional therapies.

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

Research has shown that HMBD-002 targets a protein called VISTA, which some cancers use to evade the immune system. In early studies, a patient with advanced triple-negative breast cancer experienced a 27% reduction in tumor size after five weeks of treatment with HMBD-002 alone. This suggests that HMBD-002 might be effective against tumors with VISTA, such as triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). In this trial, some participants will receive HMBD-002 as a monotherapy.

Pembrolizumab, also known as KEYTRUDA®, has proven effective in treating various cancers, including NSCLC. In this trial, other participants will receive a combination of HMBD-002 and Pembrolizumab. Combining these drugs aims to enhance the immune system's ability to fight cancer. The combination targets two different mechanisms by which cancer cells evade the immune system, potentially increasing treatment effectiveness. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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 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]

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 (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, 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) 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]

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]

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]

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]

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