APX005M + Pembrolizumab for Melanoma

Overseen By Adi Diab, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immune checkpoint inhibitors

Disqualifiers: Autoimmune disease, Heart failure, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for metastatic melanoma, a type of skin cancer that has spread. Researchers aim to determine the highest safe dose of APX005M (an experimental treatment) when combined with pembrolizumab and assess if this pairing can effectively manage the cancer. The trial will also evaluate the safety of this combination. Suitable candidates should have melanoma that cannot be surgically removed and is measurable, with at least two tumors that can be directly injected. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy higher than a physiologic dose or have received certain immune therapies recently, you may not be eligible. It's best to discuss your current medications with the study doctor.

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

Research shows that the combination of APX005M and pembrolizumab is generally well tolerated by patients. Studies have found that this treatment mix is manageable and shows promise in fighting tumors. Most people who received this combination handled it well, with no severe side effects commonly reported.

The FDA has already approved pembrolizumab for treating advanced skin cancer, providing some reassurance about its safety. APX005M is still under study, but early research suggests that, when used with pembrolizumab, it does not cause major safety concerns.

In summary, the available evidence suggests that the combination of APX005M and pembrolizumab is safe, with good tolerance and encouraging results in controlling cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of APX005M and Pembrolizumab for treating melanoma because it offers a unique approach by combining two different mechanisms of action. Unlike most treatments that rely solely on immune checkpoint inhibitors like Pembrolizumab, which helps the immune system recognize and attack cancer cells, APX005M is a CD40 agonist that further activates immune cells, potentially enhancing the body's immune response against tumors. This dual-action strategy could lead to more effective and durable responses in patients compared to standard treatments. Additionally, APX005M is delivered directly into the tumors, which may increase its effectiveness and reduce systemic side effects.

What evidence suggests that the combination of APX005M and pembrolizumab could be effective for metastatic melanoma?

Research has shown that combining APX005M with pembrolizumab, as studied in this trial, may help treat metastatic melanoma. Studies indicate that this combination effectively activates the immune system and is generally safe for patients. Early results suggest promising antitumor activity, meaning it helps fight cancer cells. Pembrolizumab is already approved for treating metastatic melanoma and works by helping the immune system attack cancer. APX005M remains experimental, but it may boost immune responses, offering hope for better disease control. ^{1 3 6 7 8}

Who Is on the Research Team?

Adi Diab

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This study is for adults with metastatic melanoma that has spread and hasn't been treated with pembrolizumab or similar drugs before. Participants need to have good liver function, not be pregnant, agree to use contraception, and have a performance status indicating they are relatively active. They should not have had recent cancer treatments or surgeries, no history of certain heart conditions or severe infections.

Inclusion Criteria

I agree to use effective birth control during and for 4 months after the study.

Your hemoglobin level is higher than 9 grams per deciliter.

I have at least two melanoma lesions that can be injected, each larger than 10 mm.

Exclusion Criteria

I have not had a blood clot in an artery in the last 3 months.

I've only had certain skin cancers, in-situ cervical cancer, non-anaplastic thyroid cancer, or have been cancer-free for 2 years.

You have a condition that weakens your immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Dose Escalation

Participants receive APX005M at escalating doses to determine the maximum tolerated dose, in combination with pembrolizumab

12 weeks

Weekly visits for drug administration and monitoring

Dose Expansion

Participants receive APX005M at the maximum tolerated dose determined in the Dose Escalation phase, in combination with pembrolizumab

12 weeks

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Scans every 8-12 weeks, phone calls every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• APX005M
• Pembrolizumab

Trial Overview The trial is testing the highest dose of APX005M that can be safely given with FDA-approved pembrolizumab in patients with metastatic melanoma. The aim is to see if this drug combination helps control the disease better than current treatments. All participants will receive both drugs at MD Anderson Cancer Center.

How Is the Trial Designed?

Group I: APX005M + Pembrolizumab Experimental Treatment 2 Interventions

Dose Escalation Phase: Starting dose level of APX005M is 0.1 mg injected directly into 1-3 tumors every 3 weeks (Weeks 0, 3, 6, and 9) for up to 4 doses. Tumor site chosen based on volume to be injected. All participants receive Pembrolizumab at 2 mg/kg by vein 1 time every 3 weeks (Weeks 0, 3, 6, 9, and 12). First dose of Pembrolizumab given 1-2 days before or after first dose of APX005M. Dose Expansion Phase: Starting dose level of APX005M is maximum tolerated dose from Dose Escalation Phase. Participants receive same dosage of Pembrolizumab as in Dose Escalation Phase.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Pyxis Oncology

Collaborator

Trials

1

Recruited

30+

Apexigen, Inc.

Industry Sponsor

Trials

12

Recruited

630+

Apexigen America, Inc.

Industry Sponsor

Trials

12

Recruited

630+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02706353

APX005M in Combination With Systemic Pembrolizumab ... The goal of Part 2 of this study is to learn if the combination can help to control metastatic melanoma. The safety of this drug combination will also be ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/newsapexigens-apx005m-combination-therapy-phase-iii-trial-for-melanoma-begins-enrollment-5768572/

Apexigen begins enrolment in APX005M combination ... Apexigen chief medical officer Ovid Trifan said: "APX005M has demonstrated robust immune system activation and an excellent safety profile and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10767304/

A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab ... The 6.5-year survival rate for ipilimumab plus nivolumab approaches 50%, with a median overall survival (OS) of 72.1 months (1). The mechanisms responsible for ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT229391

Phase I/II dose escalation and expansion cohort safety ... ... APX005M in combination with systemic pembrolizumab for treatment naive metastatic melanoma. Phase I/II dose escalation and expansion cohort safety and efficacy ...

5. onclive.com onclive.com/view/sotigalimab-pembrolizumab-combo-continues-to-show-clinical-activity-in-frontline-melanoma

Sotigalimab/Pembrolizumab Combo Continues to Show ... The combination of sotigalimab (APX005M) and pembrolizumab (Keytruda) showed encouraging antitumor activity and was well tolerated in the ...

6. pyxisoncology.com pyxisoncology.com/wp-content/uploads/publications/2019-09_cicon_poster-apx005m-003_in_melanoma_salah.pdf

Intratumoral CD40 Agonist (APX005M) in Combination with ... APX005M in combination with Pembrolizumab is well tolerated. •. APX005M in combination with Pembrolizumab showed encouraging anti-tumor activity. •. Preliminary ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT02706353

APX005M in Combination With Systemic Pembrolizumab ... Efficacy: The objective response rate (ORR) was 47% (n=32) in all patients, including patients enrolled in the dose escalation portion of the trial. At the ...

8. targetedonc.com targetedonc.com/view/sotigalimab-pembrolizumab-combo-shows-safety-and-broad-immune-activity-in-metastatic-melanoma

Sotigalimab/Pembrolizumab Combo Shows Safety and ... Seventeen percent reported stable disease and 33% reported disease progression. The disease control rate was 67% and the response rate at the ...