ADG126 + Pembrolizumab for Advanced Cancer

Recruiting at 18 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

Trial Summary

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.

What data supports the effectiveness of the drug ADG126 + Pembrolizumab for advanced cancer?

Pembrolizumab, one of the drugs in the treatment, has shown effectiveness in improving survival and response rates in various cancers, such as non-small cell lung cancer and colorectal cancer, by helping the immune system attack cancer cells. ^{1 2 3 4 5}

Is the combination of ADG126 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments 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. While specific safety data for ADG126 is not provided, pembrolizumab's safety profile is well-documented in other cancer treatments. ^{1 2 6 7 8}

What makes the drug ADG126 + Pembrolizumab unique for advanced cancer?

This treatment combines ADG126 with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. Pembrolizumab is already used for various cancers, but combining it with ADG126 may enhance its effectiveness, offering a novel approach for advanced cancer where standard treatments may not be available. ^{1 2 5 6 9}

What is the purpose of this trial?

This trial is testing a combination of two drugs, ADG126 and Pembrolizumab, in patients with advanced or metastatic solid tumors. ADG126 helps activate immune cells to attack cancer by targeting a specific protein. Pembrolizumab boosts the immune response by blocking another protein that usually stops immune cells from attacking cancer. The goal is to see if this combination is safe and effective for these patients.

Research Team

Jiping Zha, MD, PhD

Principal Investigator

Adagene Inc

Eligibility Criteria

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.

History of significant immune-mediated AE

Timeline

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

Treatment Details

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.

Participant Groups

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

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, 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]

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]

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]

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

PD-1 Inhibitor Bests Chemo for Colorectal Cancer. [2021]

4. United States 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. [2021]

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

New Approved Use for Keytruda. [2022]

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

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

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

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

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

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

9. England 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. [2021]