ADU-1805 +/- Pembrolizumab for Cancer

Recruiting at 2 trial locations

Overseen By Sairopa Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sairopa B.V.

Must not be taking: Biological agents, Chemotherapy

Disqualifiers: Melanoma, Brain tumors, Sarcoma, others

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

Compensation: Varies

Number of Visits: 6

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This first-in-human, open-label, multicenter, multi-arm dose-escalation study is designed to evaluate the safety, PK, and PD of ADU-1805, an anti- SIRPα monoclonal antibody, as monotherapy and in combination with pembrolizumab (anti-PD-1 antibody).

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as biological agents, chemotherapy, and immunotherapies, for a specific period (21 to 42 days) before the first dose. You should discuss your current medications with the trial team to see if they are affected.

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

Pembrolizumab has been shown to improve survival rates in patients with certain types of lung cancer and melanoma. It works by helping the immune system attack cancer cells, and has been approved for use in these conditions based on studies showing significant improvements in patient outcomes compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of ADU-1805 and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA or MK-3475) 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 thyroid problems and rare cases of type 1 diabetes. Safety data specific to ADU-1805 is not provided, so it's important to consult with a healthcare provider for more information. ^{1 5 6 7 8}

What makes the drug ADU-1805 combined with Pembrolizumab unique for cancer treatment?

The combination of ADU-1805 with Pembrolizumab is unique because Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells, and combining it with ADU-1805 may enhance this effect, potentially offering a new approach for cancers that do not respond well to existing treatments. ^{1 2 4 5 6}

Eligibility Criteria

Adults with advanced solid tumors that have not responded to standard treatments or for which no standard treatment is available can join. They must be over 18, able to consent, have a certain level of physical function (ECOG status 0 or 1), and adequate organ/marrow function. Not eligible if they have specific cancers like melanoma or brain tumors, are pregnant/breastfeeding, recently received certain therapies, suffer from severe infections or heart disease, among other exclusions.

Inclusion Criteria

I am 18 years old or older.

My cancer is advanced, cannot be surgically removed, and does not respond to standard treatments.

Signed and dated informed consent form

Exclusion Criteria

I have melanoma, brain tumor, glioblastoma, sarcoma, or pancreatic cancer.

Pregnancy or breast-feeding

I haven't had certain cancer treatments or drugs recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Dose Escalation

ADU-1805 monotherapy dose escalation following an i3+3 design until the RP2D is defined

Up to 2 years

Every 3 weeks (Q3W)

Combination Dose Escalation

ADU-1805 plus pembrolizumab dose escalation following an i3+3 design until the RP2D for the combination is defined

Up to 2 years

Every 3 weeks (Q3W)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2.5 years

Treatment Details

Interventions

• ADU-1805
• Pembrolizumab

Trial Overview The trial is testing ADU-1805 alone and combined with Pembrolizumab in patients with advanced solid tumors. It's the first time humans will receive ADU-1805; researchers want to see how safe it is and how the body processes it (pharmacokinetics). The study involves gradually increasing doses to find the right amount that's both effective and safe.

Participant Groups

Group I: Monotherapy dose escalation, IV, Q3W, multiple dose levels Experimental Treatment 1 Intervention

ADU-1805 monotherapy dose escalation

Group II: Combination dose escalation, IV, Q3W, multiple dose levels, pembrolizumab at fixed dose Experimental Treatment 2 Interventions

ADU-1805 plus pembrolizumab dose escalation

Who Is Running the Clinical Trial?

Sairopa B.V.

Lead Sponsor

Trials

1

Recruited

90+

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]

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]

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, 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 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 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]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

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. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

3. 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]

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

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

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

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]