ADG126 + Pembrolizumab for Advanced Cancer

Recruiting at 28 trial locations

Overseen By Xiaohong She, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Adagene Inc

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Pregnancy, CNS disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 21

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced or metastatic solid tumors, which are cancers that have spread beyond the original site. Researchers aim to determine if combining two drugs, ADG126 (Muzastotug) and pembrolizumab (KEYTRUDA®), with other medications can effectively combat tumors while assessing the safety and side effects of these combinations. The trial seeks participants whose cancer has progressed after all standard treatments or for whom no other treatments exist. Those with a solid tumor unresponsive to other treatments might find this trial a suitable option. 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 combination.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) from previous antitumor therapies and any investigational drugs. If you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them if they exceed 10 mg/day of prednisone or equivalent.

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

Research has shown that combining ADG126 with pembrolizumab appears safe. In an earlier study, fewer than 20% of patients experienced serious side effects when these drugs were used together, indicating that most patients tolerated the treatment well. ADG126 is designed to work primarily in the tumor area, potentially reducing side effects elsewhere in the body. This approach aims to enhance safety while effectively targeting cancer cells.

Pembrolizumab, also known as Keytruda®, has FDA approval for treating other cancers, providing some reassurance about its safety. Although its use with ADG126 remains under study, the initial safety results are promising for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because ADG126 and Pembrolizumab (KEYTRUDA®) are bringing innovative approaches to tackling advanced cancer. ADG126 is a novel therapy that enhances the immune system's ability to fight cancer, potentially working in synergy with Pembrolizumab, an established immunotherapy that blocks the PD-1 pathway, allowing the immune system to better attack cancer cells. Additionally, the combinations with standard care options such as Trifluridine/Tipiracil-Bevacizumab and Fruquintinib aim to boost overall effectiveness, offering new hope for patients who are not responding to existing treatments. These unique combinations could provide more effective and personalized options compared to standard treatments that primarily focus on chemotherapy and targeted therapies.

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

Research has shown that combining ADG126 with pembrolizumab may help treat advanced cancers. In this trial, participants will receive different combinations of these drugs. One arm will evaluate ADG126 and pembrolizumab with Trifluridine/Tipiracil-Bevacizumab, while another will assess their combination with fruquintinib. A third arm will study ADG126 with pembrolizumab alone. Previous studies demonstrated that the combination of ADG126 and pembrolizumab significantly shrank tumors in nearly a third of patients with a specific type of colorectal cancer, called MSS CRC. On average, these patients lived for 19.4 months, longer than expected for this group. Additionally, when ADG126 was used with pembrolizumab, fewer than 20% of patients experienced serious side effects. These early results are promising for those considering this treatment option. ^{1 2 3 4 6}

Who Is on the Research Team?

Jiping Zha, MD, PhD

Principal Investigator

Adagene Inc

Are You a Good Fit for This Trial?

Adults over 18 with advanced or metastatic solid tumors that have worsened after standard treatments, or when no other standard treatments are available. Participants must be in good physical condition (ECOG status 0 or 1), have at least one measurable tumor, and adequate organ function. A recent tumor biopsy is needed for enrollment.

Inclusion Criteria

My advanced cancer has not responded to standard treatments.

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

I have never received immunotherapy.

Exclusion Criteria

My cancer has spread to my brain or spinal cord.

I am not on high doses of steroids or other immune-weakening medicines.

Treatment with any investigational drug within washout period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Expansion

Participants receive escalating doses of ADG126 in combination with pembrolizumab to evaluate safety, tolerability, and preliminary efficacy

9 months

Every 21 days per treatment cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• ADG126
• Pembrolizumab

Trial Overview The trial tests a combination of ADG126 and Pembrolizumab to assess safety, tolerability, how the body processes the drugs (pharmacokinetics), and immune response in patients with advanced cancer. It's an early-phase study where doses will be increased to find the right balance between effectiveness and safety.

How Is the Trial Designed?

Group I: ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®) Experimental Treatment 2 Interventions

An IV infusion of ADG126 over 60-90 minutes will be administered 30-60 minutes after administration of pembrolizumab (KEYTRUDA®) infusion. A treatment cycle will consist of 21 days. ADG126 and Pembrolizumab (KEYTRUDA®) combination treatment both will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.

Group II: ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib Experimental Treatment 3 Interventions

To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Fruquintinib) while assessing safety and tolerability. The dose strength for treatment will be based on the IB and protocol. Fruquintinib (Fruzaqla) is orally given once daily for the first 21 days of each 28-day cycle. Each treatment cycle consists of 14 days. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.

Group III: ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab Experimental Treatment 3 Interventions

To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Trifluridine/Tipiracil-Bevacizumab) while assessing safety and tolerability. Standard of care treatment will be administered according to the specifications outlined in the Investigational Brochure. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.

Who Is Running the Clinical Trial?

Adagene Inc

Lead Sponsor

Trials

12

Recruited

1,000+

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

Published Research Related to This Trial

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]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

The KEYNOTE-177 study demonstrated that pembrolizumab significantly improves progression-free survival compared to the current standard of care for patients with metastatic colorectal cancer that has DNA mismatch repair or microsatellite instability-high.

This finding suggests that pembrolizumab could be a more effective first-line treatment option for this specific type of colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Inhibitor Bests Chemo for Colorectal Cancer. [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 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) 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]

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) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

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]

Citations

1. investor.adagene.com investor.adagene.com/news-releases/news-release-details/adagene-announces-updated-data-phase-1b2-study-muzastotug-adg126

Adagene Announces Updated Data from Phase 1b/2 Study of ... The 20 mg/kg Q6W dose has demonstrated a significant reduction in treatment-related toxicities - with fewer than 20% Grade 3 adverse events and no ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3579

Safety and efficacy of ADG126 (an anti-CTLA-4 masking ... ADG126 in combination with pembrolizumab (Pembro) has been evaluated in a Phase 1b/2 clinical trial (NCT05405595) and we have reported outcome ...

3. targetedonc.com targetedonc.com/view/adg126-exhibits-clinical-meaningful-efficacy-in-mss-crc

ADG126 Exhibits Clinical Meaningful Efficacy in MSS CRC ADG126 combined with pembrolizumab achieved a 29% ORR and 19.4-month median OS in MSS CRC patients, surpassing historical benchmarks. The study ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.193

Update of phase 1b/2 study of muzastotug (ADG126, an ... Here we update clinical safety and efficacy of the study as result of continued dose optimization for the IO doublet therapy.

5. esmoopen.com esmoopen.com/article/S2059-7029(25)01257-8/fulltext

39O A phase Ib/II update of ADG126 (an anti-CTLA-4 ... This is a phase 1b/2, open-label, multicenter dose escalation and expansion (EXP) study. Primary endpoints are safety, tolerability, and preliminary efficacy.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02166-5/fulltext

578P Increased therapeutic index of muzastotug (ADG126) ... Muzastotug (ADG126), a masked anti-CTLA-4 antibody, in combination with pembrolizumab (pembro) enables significant clinical benefits and supports further ...