Pembrolizumab + Trebananib for Advanced Cancer

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs, Pembrolizumab (an immunotherapy drug) and Trebananib (also known as AMG386, an experimental treatment), for certain advanced cancers, including melanoma, ovarian, renal, and colorectal cancer. The goal is to evaluate the effectiveness and safety of these drugs when used together to treat these tumors. The trial seeks participants with one of these cancers, particularly if the disease has spread or previous treatments have failed. Participants should have undergone specific prior treatments, such as a certain type of therapy for kidney cancer or have an inoperable form of melanoma. This trial may be suitable for those with these cancers who have exhausted previous treatment options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Earlier studies have tested the combination of pembrolizumab and trebananib for safety in people. One study included 55 patients with various cancers, such as colorectal and ovarian cancer. The results showed that side effects were generally manageable. Common side effects included fatigue, nausea, and changes in blood test results. Serious side effects were less common but did occur, such as inflammation in different parts of the body.

Pembrolizumab is already approved for some cancers, indicating its safety is well understood. Trebananib is still under study but has been tested in similar situations. This trial is in the early stages, so researchers are still collecting detailed safety information. However, existing data suggests that the treatment could be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Trebananib for advanced cancers because this pairing offers a novel approach to treatment. Pembrolizumab, a well-known immunotherapy, works by blocking a pathway that cancer cells use to hide from the immune system. This allows the body's natural defenses to better recognize and attack the cancer. Trebananib, on the other hand, is an angiopoietin inhibitor that disrupts the blood supply tumors need to grow. By combining these two mechanisms, the treatment has the potential to both enhance immune response and starve the tumor, offering a dual-pronged attack that is different from many current therapies that often focus on just one of these strategies.

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

This trial will evaluate the combination of pembrolizumab and trebananib for various advanced cancers. Studies have shown that pembrolizumab effectively treats advanced melanoma, helping patients live longer than with standard chemotherapy. Pembrolizumab boosts the immune system to find and fight cancer cells. Trebananib stops new blood vessels from forming, which tumors need to grow. Early research combining these two drugs in patients with colorectal, ovarian, and kidney cancers showed promise in shrinking tumors. This combination could potentially improve outcomes for several types of advanced cancers by attacking the tumor in different ways. ^{1 2 3 4 6}

Who Is on the Research Team?

Stephen Hodi

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, specifically melanoma, ovarian, renal, or colorectal cancer. Participants must have tried certain previous treatments (like VEGF TKI for renal cell carcinoma and platinum therapy for ovarian cancer), be willing to provide tissue samples, and meet specific health criteria including organ function tests. Women of childbearing potential and men must agree to use contraception.

Inclusion Criteria

I have an incurable metastatic solid tumor confirmed by tests.

Have measurable disease based on RECIST 1.1

Be willing and able to provide written informed consent for the trial

Exclusion Criteria

I have lesions that may bleed easily.

I have been treated with trebananib or similar drugs.

I have another cancer that is getting worse or needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and AMG386 to determine safety, tolerability, and appropriate dosing

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AMG386
• Pembrolizumab

Trial Overview The trial is testing a combination of Pembrolizumab (an immunotherapy drug) and AMG386 (a drug targeting blood vessel growth in tumors) as a treatment for various advanced cancers. It aims to see how well these drugs work together against the disease.

How Is the Trial Designed?

Group I: Pembrolizumab + Trebananib (Renal Cell Carcinoma) Experimental Treatment 2 Interventions

Part 2 Dose Expansion

Group II: Pembrolizumab + Trebananib (Ovarian) Experimental Treatment 2 Interventions

Part 2 Dose Expansion

Group III: Pembrolizumab + Trebananib (Melanoma) Experimental Treatment 2 Interventions

Part 2 Dose Expansion

Group IV: Pembrolizumab + Trebananib (Colorectal) Experimental Treatment 2 Interventions

Part 2 Dose Expansion

Group V: Pembrolizumab + Trebananib Experimental Treatment 2 Interventions

Part 1 Standard 3+3 Dose Escalation

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

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]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

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]

In a study of 364 patients with advanced squamous NSCLC treated with first-line pembrolizumab-chemotherapy, the median time on treatment was 6.5 months, indicating a substantial duration of therapy in a real-world setting.

The median overall survival for these patients was 15.3 months, which aligns closely with results from clinical trials, demonstrating the efficacy of pembrolizumab-chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Pembrolizumab Plus Chemotherapy for Advanced Squamous NSCLC: Real-World Outcomes at U.S. Oncology Practices. Liu, SV., Rai, P., Wang, D., et al.[2023]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

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]

In the KEYNOTE-407 study, pembrolizumab combined with chemotherapy significantly improved overall survival (17.1 months) and progression-free survival (8.0 months) compared to placebo plus chemotherapy in patients with untreated metastatic squamous non-small cell lung cancer (NSCLC).

The study also found that patients receiving pembrolizumab plus chemotherapy had a longer time before disease progression on subsequent treatments (PFS-2), supporting its use as a standard first-line therapy, despite a similar rate of serious adverse events (grade 3 to 5) between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. Paz-Ares, L., Vicente, D., Tafreshi, A., et al.[2021]

In a phase 3 trial involving 622 patients with metastatic triple-negative breast cancer, pembrolizumab did not significantly improve overall survival compared to standard chemotherapy, with median survival times of 9.9 months for pembrolizumab and 10.8 months for chemotherapy.

Pembrolizumab showed a manageable safety profile, with fewer severe treatment-related adverse events compared to chemotherapy, suggesting it may be safer for some patients despite not demonstrating superior efficacy overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Winer, EP., Lipatov, O., Im, SA., 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]

Citations

1. fightcolorectalcancer.org fightcolorectalcancer.org/clinical-trial/nct03239145/

Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 ( ... AMG386 (Trebananib) is an anti-angiogenic drug (that is, it is aimed to prevent the formation of new blood vessels), in this case, combined with anti PD-1.

2. aacrjournals.org aacrjournals.org/cancerimmunolres/article/13/1/9/750792/A-Phase-I-Trial-of-Trebananib-an-Angiopoietin-1

A Phase I Trial of Trebananib, an Angiopoietin 1 and 2 ... A total of 55 patients (40 with colorectal cancer, 11 with ovarian cancer, and four with RCC) were treated with trebananib 30 mg/kg plus pembrolizumab and were ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01704287

NCT01704287 | Study of Pembrolizumab (MK-3475) ... This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL)

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39348472/

A Phase I Trial of Trebananib, an Angiopoietin 1 and 2 ... This multicenter trial enrolled patients with metastatic ovarian cancer or MSS colorectal cancer. Trebananib was administered intravenously weekly for 12 weeks.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03239145?cond=Cancer&aggFilters=funderType%3Aindustry%2CstudyType%3Aint

NCT03239145 | Pembrolizumab (Anti-PD-1) and AMG386 ... This research study is studying an investigational combination of drugs as a possible treatment for advanced solid tumors: melanoma, ovarian, renal, or ...

6. withpower.com withpower.com/trial/phase-1-neoplasms-7-2017-fcd30

Pembrolizumab + Trebananib for Advanced Cancer Pembrolizumab is a unique drug because it is a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells, and it has shown effectiveness ...