ANV600 + Pembrolizumab for Solid Tumors

Recruiting at 17 trial locations

Overseen By Medical Director, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Anaveon AG

Must not be taking: IL-2 analogues, Immunosuppressants

Disqualifiers: Pancreatic cancer, Adrenal insufficiency, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

240 Participants Needed

Trial Summary

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, it mentions that you should not have taken any investigational agents or certain cancer therapies within a specific time before starting the trial. It's best to discuss your current medications with the trial team to get a clear answer.

What data supports the effectiveness of the drug ANV600 + Pembrolizumab for solid tumors?

Research shows that pembrolizumab, when combined with other drugs like lenvatinib, has demonstrated strong antitumor activity and durable responses in various solid tumors. This suggests that combining pembrolizumab with other treatments, like ANV600, could potentially be effective for solid tumors. ^{1 2 3 4 5}

What safety information is available for ANV600 + Pembrolizumab in solid tumors?

There is no specific safety data available for ANV600 + Pembrolizumab, but pembrolizumab alone has been shown to be generally well tolerated with common side effects like fatigue, rash, itching, and diarrhea. However, it can also cause less common but serious immune-related side effects, such as inflammation of the heart, thyroid issues, and lung inflammation, so close monitoring is recommended. ^{2 6 7 8 9}

How is the drug ANV600 + Pembrolizumab different from other treatments for solid tumors?

The combination of ANV600 and pembrolizumab is unique because it potentially offers a novel approach by combining a new agent, ANV600, with pembrolizumab, an established immune checkpoint inhibitor, to enhance immune response against solid tumors. This combination may provide a new option for patients with limited treatment choices. ^{2 4 10 11 12}

What is the purpose of this trial?

The purpose of study ANV600-001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity and antitumor activity of ANV600 administered as a single agent or in combination with pembrolizumab in adult participants with advanced solid tumors.

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors who have a life expectancy of at least 3 months. They must be able to follow the study plan and have certain levels of blood cells and kidney function. People can't join if they are too sick (with an ECOG performance status over 1) or don't meet other health requirements.

Inclusion Criteria

I have signed the consent form for this trial.

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

I can follow the study's requirements as determined by the research team.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ANV600 as a single agent or in combination with pembrolizumab to evaluate safety, tolerability, and anti-tumor activity

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ANV600
• ANV600 + pembrolizumab

Trial Overview The study is testing ANV600 alone or combined with pembrolizumab in treating advanced solid tumors. It aims to understand how safe these treatments are, how the body processes them, and their effectiveness against cancer.

Participant Groups

Group I: ANV600 single agent Experimental Treatment 1 Intervention

Group II: ANV600 in combination with pembrolizumab (KEYTRUDA®) Experimental Treatment 1 Intervention

ANV600 is already approved in United States for the following indications:

Approved in United States as ANV600 for:

• Advanced solid tumors (under investigation)

Who Is Running the Clinical Trial?

Anaveon AG

Lead Sponsor

Trials

5

Recruited

340+

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 2 study involving 38 patients with pleural mesothelioma, the combination of pembrolizumab and lenvatinib resulted in a promising objective response rate of 58%, indicating significant anti-tumor activity after prior chemotherapy.

However, the treatment was associated with considerable toxicity, with 26% of patients experiencing serious treatment-related adverse events, including one death, highlighting the need for careful monitoring and supportive care during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. Douma, LH., Lalezari, F., van der Noort, V., et al.[2023]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

In a study of 145 patients with PD-L1 strongly positive non-small-cell lung cancer (NSCLC), those with higher PD-L1 expression (≥ 75%) experienced better treatment outcomes with pembrolizumab, showing a higher objective response rate (51% vs. 33%) and longer progression-free survival (13.9 months vs. 5.2 months).

Patients with liver metastasis had significantly poorer responses to pembrolizumab, with an objective response rate of only 20% compared to 47% in those without liver metastasis, indicating that both PD-L1 expression and liver metastasis are important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. Takeyasu, Y., Yoshida, T., Shibaki, R., et al.[2021]

In a study involving 351 patients with advanced noncolorectal MSI-H/dMMR solid tumors, pembrolizumab showed a significant objective response rate (ORR) of 30.8%, indicating its efficacy in this patient population.

The treatment demonstrated a long median duration of response of 47.5 months and manageable safety, with only 11.1% of patients experiencing severe (grade 3-4) treatment-related adverse events, supporting its use in heavily pretreated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Maio, M., Ascierto, PA., Manzyuk, L., et al.[2022]

In a study of 183 patients with advanced melanoma treated with pembrolizumab, several baseline factors such as active brain metastases, higher total metabolic tumor volume (TMTV), and lower absolute lymphocyte count (ALC) were linked to worse survival outcomes.

TMTV was identified as a more effective predictor of treatment futility compared to other markers like C-reactive protein (CRP) and lactate dehydrogenase (LDH), suggesting that patients with high TMTV may not benefit from pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. Awada, G., Jansen, Y., Schwarze, JK., et al.[2021]

In a study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab and pemetrexed-carboplatin (PC) significantly improved the objective response rate (56.7% vs. 30.2% with PC alone) and progression-free survival (PFS) compared to PC alone, with a hazard ratio (HR) of 0.53.

The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival benefit, although 41% of patients experienced grade 3 to 5 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. Borghaei, H., Langer, CJ., Gadgeel, S., et al.[2022]

In a phase 2 study involving 112 patients with advanced anal squamous cell carcinoma, pembrolizumab demonstrated an objective response rate of 11%, with a higher response (15%) in patients with PD-L1-positive tumors, indicating its potential efficacy in this difficult-to-treat cancer.

The treatment was generally well-tolerated, with 61% of patients experiencing treatment-related adverse events, but no treatment-related deaths were reported, suggesting a favorable safety profile for pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Marabelle, A., Cassier, PA., Fakih, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor used for non-small-cell lung cancer, can lead to severe immune-related side effects, including acute myocarditis and complete atrioventricular block, as seen in a case study.

The case highlights the importance of close cardiac monitoring for patients receiving pembrolizumab, especially when treated in an outpatient setting, due to the potential for serious heart-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Atrioventricular Block Associated with Pembrolizumab-induced Acute Myocarditis: The Need for Close Cardiac Monitoring. Katsume, Y., Isawa, T., Toi, Y., et al.[2018]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab (P) can be safely combined with various chemotherapy agents, including gemcitabine and liposomal doxorubicin, in patients with advanced solid tumors, as shown in a phase Ib trial involving 49 patients.

The combination treatment resulted in eight partial responses across different tumor types, indicating potential efficacy, but further studies are needed to confirm if the response duration is better than chemotherapy or immunotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Weiss, GJ., Waypa, J., Blaydorn, L., et al.[2022]

In a phase II trial involving 50 patients with early triple-negative breast cancer, 66% achieved a pathological complete response (pCR) after treatment with nab-paclitaxel and pembrolizumab, indicating a promising efficacy of this combination therapy.

The treatment was associated with manageable side effects, with fatigue, peripheral sensory neuropathy, and neutropenia being the most common adverse events, suggesting that this regimen could be a viable alternative to platinum-based chemotherapy for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Fasching, PA., Hein, A., Kolberg, HC., et al.[2023]

In a phase Ib trial (KEYNOTE-028) involving 43 patients with advanced anal carcinoma, pembrolizumab showed a manageable safety profile, with 64% experiencing treatment-related adverse events, but no treatment-related deaths or discontinuations.

Among patients with PD-L1-positive tumors, pembrolizumab achieved a 17% overall response rate and a 58% disease control rate, indicating promising antitumor activity and supporting further research in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ott, PA., Piha-Paul, SA., Munster, P., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. [2023]

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

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]

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

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. [2021]

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

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. [2021]

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

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

Complete Atrioventricular Block Associated with Pembrolizumab-induced Acute Myocarditis: The Need for Close Cardiac Monitoring. [2018]

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

Pembrolizumab in the management of metastatic melanoma. [2020]

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

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). [2022]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). [2023]

12. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. [2021]