ADU-1805 +/- Pembrolizumab for Cancer

Recruiting at 11 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ADU-1805, tested alone and with pembrolizumab (an immunotherapy drug), to assess its safety and effectiveness for people with advanced solid tumors unresponsive to other treatments. The trial aims to understand how the body processes these drugs and their potential in fighting cancer. Suitable participants have solid tumors untreatable with standard therapies and have not recently received certain treatments. 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 treatment.

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.

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

Research shows that ADU-1805, a type of antibody, is in the early stages of testing for human safety. Currently, detailed safety information is unavailable for ADU-1805 alone or in combination with pembrolizumab. Pembrolizumab, also known as Keytruda, has FDA approval for treating several cancer types and has been effective and generally well-tolerated, though some may experience side effects like tiredness, skin rash, or nausea.

In this testing phase for ADU-1805, researchers are assessing how well people tolerate the new drug. They closely monitor for any side effects or negative reactions while trying different doses. Since this is the first human test of ADU-1805, no previous studies provide safety information. Prospective participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ADU-1805, both as a monotherapy and in combination with pembrolizumab, because it targets cancer in a novel way. Unlike existing treatments that primarily focus on interrupting specific cancer cell pathways, ADU-1805 is designed to enhance the immune system’s ability to recognize and attack cancer cells. This unique mechanism could potentially lead to more effective outcomes for patients whose cancers are resistant to other therapies. Furthermore, when combined with pembrolizumab, an established immunotherapy, there is potential for a synergistic effect that could improve efficacy beyond current standard treatments.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that pembrolizumab, a current cancer treatment, has a strong track record. It has improved the five-year survival rate to about 19% for some lung cancer patients, surpassing chemotherapy alone. In this trial, some participants will receive ADU-1805, the new treatment under study, as a monotherapy. ADU-1805 is a monoclonal antibody that targets a protein called SIRPα, which helps cancer cells evade the immune system. Early research suggests that ADU-1805 can activate immune cells like neutrophils and macrophages, which are crucial for fighting cancer. Other participants will receive a combination of ADU-1805 with pembrolizumab, which may further enhance the immune system's ability to combat cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 fully active or can carry out light work.

Signed and dated informed consent form

Measurable disease according to RECIST (Safety Expansion only)

Exclusion Criteria

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

Pregnancy or breast-feeding

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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, 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05856981?term=Phase%201%20Study%20Evaluating%20the%20Safety%20and%20PK%20of%20ADU-1805%20in%20Advanced%20Solid%20Tumors&rank=1

Phase 1 Study Evaluating the Safety and PK of ADU-1805 ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31801627/

Functional characterization of the selective pan-allele anti- ... The humanized monoclonal IgG2 antibody ADU-1805 binds to all known human SIRPα alleles, showing minimal binding to SIRPβ1, while cross-reacting with SIRPγ.

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-and-sairopa-announce-us-fda-clears-investigational-new

Exelixis and Sairopa Announce US FDA Clears ... ADU-1805 is a potential best-in-class monoclonal antibody targeting SIRPα to block the SIRPα-CD47 checkpoint –. – Phase 1 study of ADU-1805 ...

4. jitc.bmj.com jitc.bmj.com/content/7/1/340

Functional characterization of the selective pan-allele anti- ... Our data suggest that SIRPα targeting by ADU-1805 can activate myeloid cell types such as neutrophils and macrophages. The role of neutrophils ...

5. sairopa.com sairopa.com/sairopa-clinical-milestone-adu1805-exelixis/

Sairopa Achieves $35M Clinical Milestone with Exelixis for ... (Nasdaq: EXEL) involving ADU-1805, an innovative anti-SIRPα antibody with the potential to enhance the immune system's ability to combat cancer.

6. ctv.veeva.com ctv.veeva.com/study/phase-1-study-evaluating-the-safety-and-pk-of-adu-1805-in-advanced-solid-tumors

Phase 1 Study Evaluating the Safety and PK of ADU-1805 in ... This first-in-human, open-label, multicenter, multi-arm dose-escalation study is designed to evaluate the safety, PK, and PD of ADU-1805, ...