ADG116 + Immunotherapy for Cancer

Not currently recruiting at 4 trial locations

Overseen By Jiping Zha

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adagene Inc

Must not be taking: Corticosteroids, G-CSF

Disqualifiers: Pregnancy, Autoimmune disease, CNS 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment using a drug called ADG116, which targets a specific protein on immune cells to potentially enhance the body's ability to fight tumors. The study tests ADG116 alone and in combination with either another drug, ADG106, or an anti-PD-1 drug (a type of immunotherapy). It aims to assist people with advanced or spreading solid tumors who have exhausted all standard treatments. Participants must have at least one measurable tumor and adequate organ function. 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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like corticosteroids or granulocyte colony stimulating factor (G-CSF) close to the start of the trial.

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

Research has shown that ADG116, when used alone, is generally safe for patients with advanced solid tumors. Patients have tolerated various doses, even higher ones, without major issues.

When combined with ADG106, early studies suggest ADG116 remains safe. ADG106 alone has also demonstrated safety and effectiveness in early trials.

For the combination of ADG116 with an anti-PD-1 drug like pembrolizumab, studies have found no serious side effects that would prevent dose escalation. The most common side effect was mild nausea.

Overall, these findings suggest that ADG116, whether used alone or with other drugs, is well-tolerated by patients. This trial is in its early stages, focusing primarily on assessing the safety and tolerability of the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ADG116 because it takes a novel approach to fighting cancer. Unlike many current cancer treatments that focus on directly killing cancer cells, ADG116 works by enhancing the body's immune response. It's combined with other immunotherapies like ADG106 or an anti-PD1 drug to potentially boost this effect even further. This unique mechanism of action could offer a new hope for patients, bringing a more targeted and potentially less toxic treatment option compared to traditional chemotherapy.

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

Research has shown that ADG116, a type of human-made antibody, may help treat advanced solid tumors. In this trial, participants may receive ADG116 as a monotherapy. Studies have found it effective on its own, managing various doses without causing serious side effects. Another group in this trial will receive a combination of ADG116 with another antibody, ADG106, which has demonstrated an even stronger ability to fight tumors. Early tests showed that this combination led to better outcomes, including complete remission in some head and neck cancer cases. Additionally, some participants will receive ADG116 combined with anti-PD-1 drugs. Initial results have shown strong effects in certain cancers like MSS-CRC, with a good safety record. Overall, these findings suggest that ADG116, whether used alone or with other treatments, could be an important option for cancer therapy. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors who've exhausted standard treatments or can't access them may join this trial. They should have a life expectancy over 12 weeks, be relatively healthy (ECOG status 0-1), and have at least one measurable tumor lesion. Prior therapies must be completed at least 4 weeks before the study starts, and they shouldn't have severe previous side effects from similar drugs.

Exclusion Criteria

Patients who meet any of the following criteria cannot be enrolled: Pregnant or breastfeeding females. Females of childbearing potential and males whose partners are of childbearing potential who do not agree to the use of 2 forms of highly effective contraception during the treatment period and for 120 days after the last dose of study drug. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug. Grade ≥ 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Central nervous system disease involvement (but allow patients with prior brain metastases treated at least 4 weeks prior to the first dose of ADG116 that are clinically stable and do not require chronic corticosteroid treatment to be enrolled in the study), or prior history of NCI CTCAE Grade ≥ 3 drug-related CNS toxicity. History of life-threatening hypersensitivity or known to be allergic to protein drugs or recombinant proteins or any ingredients contained in the ADG116 drug formulation. Patients with active autoimmune disease or a documented medical history of autoimmune disease or symptoms (including celiac disease) that required systemic use of pharmacologic dose of corticosteroid and/or immunosuppressant. Exceptions are patients with vitiligo, resolved childhood asthma/atopy, and type 1 diabetes mellitus or hypothyroidism that can be managed by replacement therapy, or any other autoimmune condition upon discussion with Medical Monitor and the Sponsor. Patients requiring systemic treatment with corticosteroids (> 15 mg/day prednisone or equivalent) or other immunosuppressive medications within 21 days before the planned first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 15 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Ophthalmologic, nasal, inhaled and intra-articular injections of steroids are allowed. Peripheral neuropathy Grade ≥ 2. Patients receiving granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin, or blood (red blood cell [RBC] or platelet) transfusion within 14 days prior to the first dose of the study drug. Active viral (any etiology) hepatitis patients are excluded. Hepatitis B virus (HBV) carriers are ineligible. Cured hepatitis C (HCV) (negative HCV ribonucleic acid [RNA] test) patients may be enrolled after consulting with the Medical Monitor. This criterion does not apply for HCC. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled diabetes as evidenced by screening (baseline) HgbA-1c ≥7.5, asthma, chronic obstructive pulmonary disease (COPD), or other conditions that pose a risk to the patient participating on study. Known positive test result for human immunodeficiency virus (HIV) (except the disease is clinically controlled) or acquired immune deficiency syndrome (AIDS). Patients with any type of primary immunodeficiency or autoimmune disorder requiring treatment. Major surgery within 4 weeks prior to the first dose of the study drug. Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation. Clinically significant cardiac conditions, including myocardial infarction within the last 6 months, uncontrolled angina, viral myocarditis, pericarditis, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months prior to the first dose of the study drug. Patients with underlying hemoglobinopathies (eg, thalassemia) will be excluded, this criterion only applicable to the ADG106 plus ADG116 combination groups. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug. Live viral vaccine therapies within 4 weeks prior to the first dose of study drug. Any known, documented, or suspected history of illicit substance abuse. Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgment of the Investigator might compromise the safety of the patient or integrity of the study, interfere with the patient participation in the trial or compromise the trial objectives

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive dose escalation of ADG116, either as monotherapy or in combination with ADG106 or anti-PD-1 antibody

8-12 weeks

Treatment

Participants receive the study medication, ADG116, in combination with ADG106 or anti-PD-1 antibody to evaluate safety and efficacy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADG106
• ADG116
• Anti-PD-1 Antibody

Trial Overview The trial is testing ADG116, an antibody targeting CTLA-4, which might help the immune system fight cancer. It's also looking at combining ADG116 with either ADG106 or an anti-PD-1 drug to see if these combinations are more effective in treating solid tumors than each drug alone.

How Is the Trial Designed?

Group I: Part C : Dose escalation of ADG116 combined with ADG106 Experimental Treatment 2 Interventions

Group II: Part B : Dose escalation of ADG116 combined with anti PD1 drug Experimental Treatment 2 Interventions

Group III: Part A : Dose escalation of ADG116 monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Adagene Inc

Lead Sponsor

Trials

12

Recruited

1,000+

Citations

1. investor.adagene.com investor.adagene.com/news-releases/news-release-details/adagene-announces-clinical-data-sitc-2022-anti-ctla-4-neobodytm

Adagene Announces Clinical Data at SITC 2022 on Anti-CTLA ... Preliminary update on study evaluating ADG116 in combination with pembrolizumab shows potent activity in MSS-CRC, with no dose limiting toxicities.

2. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A785

753 A phase 1b/2 study of a novel anti-CTLA-4 NEObody ... Conclusions ADG116 monotherapy has cleared multiple dose levels including 15 mpk, a dose higher than any reported anti-CTLA-4 class agents in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04501276

NCT04501276 | A Phase 1b/2 Study of ADG116, ... The enhanced antitumor efficacy results observed from the preclinical studies of ADG116 in combination with ADG106 or anti-PD-1 provided further support to ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A570

506 Deciphering improved clinical therapeutic index (TI ... Results Key clinical data are summarized in table 1. Muzastotug monotherapy at 20 mg/kg Q3W showed better safety than ADG116 at 10 mg/kg Q3W.

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04501276

A Phase 1b/2 Study of ADG116, ADG116 Combined With ... The safety and preliminary efficacy readout included patients with over 20 different tumor types, the majority (64%) of whom received three or more lines of ...

6. investor.adagene.com investor.adagene.com/node/6971/pdf

Adagene Presents Clinical Data Demonstrating Strong Safety ... promising safety profile of ADG116 monotherapy in patients with advanced solid tumors across 15 different tumor types, the majority of which are.