ADA-011 + PD(L)-1 Inhibitor for Solid Tumors

No longer recruiting at 5 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adanate, Inc

Must not be taking: Antineoplastics, Corticosteroids

Disqualifiers: CNS disease, Infections, Autoimmune, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ADA-011 for individuals with advanced solid tumors. Researchers aim to assess the safety and tolerability of ADA-011 both alone and in combination with a PD(L)-1 inhibitor, a type of cancer therapy. Participants will receive the treatment via IV every three weeks. The trial seeks individuals whose cancer has returned or is worsening and who have no remaining standard 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 therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any local or systemic cancer treatments, including chemotherapy, hormonal therapy, or radiation, at least 2 weeks before starting the trial. If you are using corticosteroids, you must not exceed 10 mg daily of prednisone or equivalent within 4 weeks before the trial.

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

Research has shown that PD-L1 inhibitors, like durvalumab, are generally safe for most patients with solid tumors. However, some individuals might experience side effects, such as lung inflammation.

For ADA-011, the current trial aims to assess its safety and tolerability. As this is an early-phase trial, researchers are still gathering information about ADA-011's safety, so data on its effects in humans remain limited.

Early-phase trials are the first step in testing new treatments in people, meaning the treatment is closely monitored for any possible side effects. Prospective participants should discuss any concerns with the research team to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because ADA-011 offers a novel approach to tackling solid tumors. Unlike many current treatments that target cancer cells directly, ADA-011 works alongside a PD(L)-1 inhibitor to potentially boost the immune system's ability to fight cancer. This combination could enhance the body's natural defenses against tumors. Additionally, ADA-011 is administered intravenously every three weeks, which might offer a more convenient schedule compared to some existing therapies that require more frequent dosing. This innovative approach has the potential to improve outcomes by harnessing the power of the immune system in a more targeted and efficient way.

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

This trial investigates ADA-011 to assess its safety and tolerability. Participants may receive ADA-011 as a monotherapy or with a PD(L)-1 inhibitor. Although human trials have provided limited information, researchers are exploring ADA-011's potential benefits for people with solid tumors. The combination therapy with a PD(L)-1 inhibitor, which enhances the immune system's ability to fight cancer, could offer a new treatment approach for these tumors. The goal is to strengthen the body's ability to combat cancer cells, potentially improving treatment outcomes. Although the research remains in early stages, the hope is that these treatments can effectively target and treat solid tumors. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be removed or have come back after treatment, and there's no standard therapy left to try. They should be fairly active (ECOG ≤2), have measurable tumor growth, and their organs must work well. People with severe autoimmune diseases, unresolved side effects from past cancer treatments (except hair loss), infections including COVID-19, recent antineoplastic therapies or surgeries, high-dose steroid use, organ transplants, brain disease involvement or serious drug-related brain toxicity are excluded.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and is getting worse despite treatment.

Measurable disease per RECIST v1.1 or per other criteria best suited for the specific tumor type being evaluated

My organs are working well.

Exclusion Criteria

I do not have any ongoing serious infections.

All my side effects from cancer treatment are mild, except for hair loss.

History or risk of severe, chronic, untreated, or currently active autoimmune disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ADA-011 monotherapy and combination therapy with a PD(L)-1 inhibitor are administered intravenously every 3 weeks at escalating doses to determine safety and tolerability

21 days (cycle 1) for initial evaluation, up to 36 months for ongoing assessment

Every 3 weeks

Dose Expansion

ADA-011 monotherapy is administered at the recommended phase 2 dose to further evaluate safety, tolerability, and preliminary efficacy

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADA-011
• PD(L)-1 inhibitor

Trial Overview The study tests ADA-011 alone and combined with a checkpoint inhibitor in people with advanced solid tumors. It starts by finding the safest dose of ADA-011 (dose escalation) and then checks its safety and early results on tumor control at this dose in more patients (dose expansion).

How Is the Trial Designed?

Group I: Combination Therapy Dose Escalation Experimental Treatment 2 Interventions

Combination therapy with ADA-011 and PD(L)-1 inhibitor (at escalating ADA-011 doses) will be administered IV Q3W, starting with Cycle 1, Day 1 in participants with histologically or cytologically confirmed solid tumors.

Group II: ADA-011 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

ADA-011 monotherapy with the preliminary recommended phase 2 dose (RP2D) of ADA-011, in participants with histologically or cytologically confirmed solid tumors.

Group III: ADA-011 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

ADA-011 monotherapy will be administered intravenously (IV), every 3 weeks (Q3W) at escalating doses starting with Cycle 1, Day 1, until participant withdrawal. Participants enroll with histologically or cytologically confirmed solid tumors.

Who Is Running the Clinical Trial?

Adanate, Inc

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

In a study of 191 patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors, those who experienced immune-related adverse events (irAEs) had significantly better treatment outcomes, with an objective response rate of 42.0% compared to 25.8% in those without irAEs.

The presence of irAEs was associated with improved progression-free survival, suggesting that these adverse events may indicate a more effective immune response to the treatment, although they did not correlate with overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China. Chen, X., Nie, J., Dai, L., et al.[2022]

A total of 686 clinical trials are currently investigating anti-PD-(L)1 agents for intrathoracic tumors, with a significant focus on non-small cell lung cancer (NSCLC), indicating a robust interest in this area of immunotherapy.

The majority (81%) of these trials are exploring combination treatments, often pairing PD-(L)1 blockade with chemotherapy or other immunotherapies, highlighting a trend towards more comprehensive treatment strategies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors. Kareff, SA., Samtani, S., Burotto, M., et al.[2022]

This study aims to create a comprehensive toxicity profile for anti-PD-1 and anti-PD-L1 drugs by analyzing systematic reviews and meta-analyses, focusing on treatment-related adverse events in cancer patients.

The research will utilize a network meta-analysis approach to synthesize data from various studies, ensuring a thorough understanding of the safety and adverse effects associated with these immunotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 and anti-PD-L1 drugs treatment-related adverse events for patients with cancer: Protocol for an overview of systematic reviews with meta-analyses. Li, J., Liu, M., Wang, J., et al.[2023]

In a study of 126 patients with EGFR-mutant non-small-cell lung cancer, 15% experienced severe immune-related adverse events (irAEs) when treated with sequential PD-(L)1 blockade followed by osimertinib, particularly within 3 months of PD-(L)1 treatment.

No severe irAEs were reported when osimertinib was administered before PD-(L)1 blockade or when PD-(L)1 was followed by other EGFR-TKIs, indicating that the severe toxicity is specifically associated with the sequence of PD-(L)1 followed by osimertinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. Schoenfeld, AJ., Arbour, KC., Rizvi, H., et al.[2023]

PD-L1 checkpoint inhibitors, like durvalumab, have shown significant efficacy in treating various solid tumors, including lung cancer and breast cancer, by suppressing tumor growth and improving patient survival.

While PD-L1 therapy is generally safe, it can cause adverse reactions such as pneumonitis and colitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab in Solid Tumors. Chen, M., Jiang, J., Chen, J., et al.[2023]

Soluble programmed death-1 ligand-1 (sPD-L1) levels were significantly higher in lung cancer patients compared to healthy controls, indicating its potential role as a biomarker for lung cancer.

Higher sPD-L1 levels were associated with more advanced stages of non-small cell lung cancer (NSCLC) and poorer overall health, suggesting that elevated sPD-L1 may indicate a negative prognosis for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of soluble programmed death-1 ligand-1 of lung cancer patients with different characteristics. Zhu, HB., Song, X.[2023]

In a meta-analysis of 12 studies involving 1188 lung cancer patients, high levels of soluble PD-L1 (sPD-L1) were linked to significantly worse overall survival (OS) and progression-free survival (PFS) in patients receiving immune checkpoint inhibitors, indicating its potential as a negative prognostic factor.

Additionally, high sPD-L1 levels were associated with poorer OS and lower objective response rates in patients treated with non-immune checkpoint inhibitor therapies, suggesting that sPD-L1 could serve as a predictive biomarker for treatment outcomes in lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble PD-L1 as a predictive biomarker in lung cancer: a systematic review and meta-analysis. Cheng, Y., Wang, C., Wang, Y., et al.[2022]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05601219

NCT05601219 | A Phase 1 Study of ADA-011 for Subjects ... This study consists of dose escalation evaluation to determine the safety and tolerability of ADA-011 as a monotherapy.

2. withpower.com withpower.com/trial/phase-1-solid-tumors-adult-9-2022-14e37

ADA-011 + PD(L)-1 Inhibitor for Solid Tumors This trial is testing ADA-011 alone and with another drug to see if it is safe and can be tolerated by patients. It focuses on people who might not respond ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12434680/

Modulating Treatment Outcomes of Patients with Solid Tumors ... To investigate the effect of concurrent medications on the treatment outcomes in patients enrolled in early-phase clinical trials evaluating ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09045

A Phase 1 Study of ADA-011 for Subjects With Advanced ... This study consists of dose escalation evaluation to determine the safety and tolerability of ADA-011 as a monotherapy.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2059702925001590

First-in-human phase I study to evaluate safety, tolerability ... The rate of ADA was 93.9% (31/33), of which 63.6% (21/33) was treatment induced and 30.3% (10/33) was treatment boosted. Conclusion. PF-07209960 was generally ...

6. ctv.veeva.com ctv.veeva.com/study/a-phase-1-study-of-ada-011-for-subjects-with-advanced-solid-tumors

A Phase 1 Study of ADA-011 for Subjects With Advanced ... This study consists of dose escalation evaluation to determine the safety and tolerability of ADA-011 as a monotherapy.

7. trials.ohsu.edu trials.ohsu.edu/s/a-phase-1-study-of-ada-011-for-subjects-with-advanced-solid-tumors-313150/

A Phase 1 Study of ADA-011 for Subjects With Advanced ... The purpose of the study is to learn more about ADA-011-001 (the study drug) in those with cancer that no longer responds to usual treatment.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04628780

Study to Test the Safety and Tolerability of PF-07209960 in ... This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and dose expansion study intended to evaluate the safety, ...