PD-1 Inhibitor for Pancreatic Cancer

No longer recruiting at 1 trial location

Overseen By Colleen Apostal, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunotherapy, Steroids

Disqualifiers: Brain metastases, Heart disease, Infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a new treatment called INCMGA00012, a PD-1 inhibitor, for individuals with specific types of advanced pancreatic or ampullary cancer. The goal is to determine if this drug can stop or slow the growth of tumors that cannot be surgically removed. It suits those who have tried at least one chemotherapy treatment but no more than two prior treatments. Individuals diagnosed with adenosquamous carcinoma of the pancreas or ampulla and have a measurable tumor may consider this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy, radiation, or biological cancer therapy within 14 days before starting the study drug, and you should not use systemic steroids within 14 days of study treatment.

Is there any evidence suggesting that INCMGA00012 is likely to be safe for humans?

Research has shown that retifanlimab (INCMGA00012) has a safety profile similar to other treatments in its category. In previous studies, patients experienced some side effects, which were expected and similar to those from other immunotherapy treatments. These side effects include symptoms like tiredness, nausea, and skin rash. Importantly, these side effects were generally manageable.

Past studies have also demonstrated that retifanlimab was well-tolerated by patients with various types of cancer, such as skin cancer (melanoma) and lung cancer. This indicates a history of safe use in people. While more information is always useful, current evidence suggests this treatment is relatively safe, with side effects that are often mild and manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about INCMGA00012 for pancreatic cancer because it represents a novel approach compared to traditional treatments like chemotherapy and radiation. Unlike these standard options, INCMGA00012 is a PD-1 inhibitor, which works by blocking a specific protein that often helps cancer cells evade the immune system. This mechanism boosts the body's natural defenses to better recognize and attack the cancer cells. Such targeted immunotherapy offers the potential for fewer side effects and improved efficacy, making it a promising new option for patients.

What evidence suggests that INCMGA00012 might be an effective treatment for pancreatic cancer?

Research has shown that INCMGA00012, also known as retifanlimab, could be helpful in treating certain cancers. In earlier studies, retifanlimab effectively targeted tumors that respond to PD-1 inhibitors, such as those in melanoma and non-small cell lung cancer. Specifically, it demonstrated a 14% response rate in patients with squamous cell anal carcinoma who had already tried other treatments. This suggests that retifanlimab might help the immune system fight cancer cells. While data collection on its effects on pancreatic cancer in this trial continues, these findings are promising for its use in other difficult-to-treat cancers. ^{4 6 7 8 9}

Who Is on the Research Team?

Nilofer Azad, MD

Principal Investigator

Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

This trial is for adults with advanced pancreatic or ampullary cancer that can't be surgically removed. Participants must have tried at least one chemotherapy, be in fairly good health (ECOG 0-1), and not have had more than two systemic treatments. They should expect to live more than three months, agree to biopsies, use birth control if applicable, and sign consent forms. People with certain medical conditions or recent treatments are excluded.

Inclusion Criteria

I have had 1 or 2 treatments for my condition, including chemotherapy.

My cancer is a specific type of pancreas or ampulla cancer.

I am HIV-positive, on effective treatment, with a CD4+ count ≥ 350 and an undetectable viral load.

Exclusion Criteria

I have a wound, ulcer, or bone fracture that is not healing.

You are using extra oxygen at home.

I have or had brain metastases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INCMGA00012, a PD-1 antibody, to evaluate clinical activity in patients with unresectable or metastatic adenosquamous pancreatic or ampullary cancer

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• INCMGA00012

Trial Overview The study tests INCMGA00012 (a PD-1 antibody) on patients who've previously treated their unresectable or metastatic adenosquamous pancreatic or ampullary cancer without success. It's a Phase 2 trial focusing on the effectiveness of this immunotherapy drug.

How Is the Trial Designed?

Group I: INCMGA00012 (PD-1 antibody) Experimental Treatment 1 Intervention

All participants received the interventional study drug; INCMGA00012.

INCMGA00012 is already approved in United States, European Union for the following indications:

Approved in United States as Zynyz for:

• Metastatic or recurrent locally advanced Merkel cell carcinoma

Approved in European Union as Zynyz for:

• Metastatic or recurrent locally advanced Merkel cell carcinoma

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

In pancreatic ductal adenocarcinoma (PDAC), a significant portion of tumor-infiltrating T cells exhibit an exhausted phenotype characterized by high levels of PD-1 and TIGIT, indicating a challenging immune environment for effective therapy.

Combining anti-PD-1 and TIGIT blockade has been shown to enhance T cell activity, suggesting that this dual approach could improve immunotherapy outcomes in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade. Pearce, H., Croft, W., Nicol, SM., et al.[2023]

The combination of galunisertib and durvalumab was found to be tolerable with no dose-limiting toxicities, and the recommended dose for further studies was established at 150 mg of galunisertib taken twice daily alongside durvalumab.

While the treatment showed a disease control rate of 25% among 32 patients, clinical activity was limited, suggesting that this combination may be more effective if used earlier in treatment or in patients selected based on specific biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer. Melisi, D., Oh, DY., Hollebecque, A., et al.[2021]

In a systematic review of 59 randomized controlled trials involving 41,757 patients, immune checkpoint inhibitors (ICIs) were found to be associated with a 0.93% incidence of all-grade pancreatitis and higher rates of pancreatic enzyme elevations, indicating a notable risk of pancreatic adverse events (AEs) during treatment.

The study revealed that PD-1 inhibitors carry a greater risk of pancreatic AEs compared to PD-L1 inhibitors, and patients receiving dual ICI therapy face an even higher risk than those on single ICI therapy, highlighting the need for clinician awareness regarding these potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis. Zhao, Z., Zhang, W., Pang, L., et al.[2023]

A study analyzing 2,364 cases of pancreatic adverse events (AEs) linked to immune checkpoint inhibitors (ICIs) found significant associations, particularly with ICI-associated pancreatitis and diabetes mellitus, indicating a notable risk for patients undergoing ICI treatment.

Combination therapy with ICIs showed a higher frequency of pancreatic AEs compared to monotherapy, suggesting that while the risk of these adverse events increases, the fatality rate remains lower, highlighting the importance of patient awareness regarding these potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A Large-Scale Pharmacovigilance Analysis. Zhang, Y., Fang, Y., Wu, J., et al.[2022]

A study analyzing 70,330 adverse events reported to the FDA found that immune checkpoint inhibitors (ICIs) significantly increase the risk of gastrointestinal (GI) toxicities, particularly colitis, hepatobiliary disorders, and pancreatitis, with colitis showing the highest reporting odds ratio of 17.2.

The risk of these GI adverse events was notably higher with anti-CTLA-4 treatments compared to anti-PD-1 and anti-PD-L1 therapies, and factors such as female gender and polytherapy were identified as strong risk factors for these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System. Bai, X., Jiang, S., Zhou, Y., et al.[2021]

The combination of ipilimumab and gemcitabine was found to be safe and tolerable for treating advanced pancreatic ductal adenocarcinoma (PDAC), with a maximum tolerated dose established at ipilimumab 3 mg/kg and gemcitabine 1,000 mg/m2.

Despite the safety of the regimen, the overall response rate was only 14%, indicating that adding ipilimumab does not significantly enhance the effectiveness compared to gemcitabine alone in advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study. Kamath, SD., Kalyan, A., Kircher, S., et al.[2022]

A meta-analysis of 53 trials involving 6581 patients revealed that combined immune checkpoint inhibitors (ICIs) lead to significant gastrointestinal adverse events, with diarrhea occurring in 25.4% of patients, hepatitis in nearly 13%, and pancreatitis in about 7.5%.

The study highlights a high incidence of both mild and severe gastrointestinal adverse events associated with combined ICI treatments, indicating a need for further research to understand these effects and their impact on patient treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal treatment-related adverse events of combined immune checkpoint inhibitors: a meta-analysis. Karna, R., S Deliwala, S., Ramgopal, B., et al.[2023]

In a case series of seven patients treated with immune checkpoint inhibitors (ICIs), two developed diabetic ketoacidosis (DKA) and five experienced pancreatitis, highlighting the potential for serious pancreatic adverse events associated with ICI therapy.

Pancreatitis was often asymptomatic and could be managed effectively by holding the ICI treatment and administering steroids, with some patients able to safely resume ICI therapy after recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events in patients treated with immune checkpoint inhibitors. Hana, C., Rehman, T., Park, K., et al.[2023]

Pancreatic ductal adenocarcinoma (PDAC) shows resistance to traditional immune checkpoint therapies (ICTs), but combining agonist 41BB and antagonist LAG3 ICTs can enhance survival and boost antitumor immunity by improving T cell activity and reducing immunosuppressive cells.

The most effective treatment strategy involved a triple therapy combining T cell-activating ICTs with a CXCR1/2 inhibitor, which led to durable complete responses in PDAC, suggesting a promising new approach for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1/CXCR2 results in antitumor immunity and durable response in pancreatic cancer. Gulhati, P., Schalck, A., Jiang, S., et al.[2023]

Citations

1. actuatetherapeutics.com actuatetherapeutics.com/press_releases/actuate-therapeutics-to-collaborate-with-incyte-corporation-and-the-university-of-pittsburgh-on-clinical-trial-of-elraglusib-in-combination-with-retifanlimab-and-mfolfirinox-in-patients-with-advanced/

Actuate Therapeutics To Collaborate with Incyte ... Initial data from this Phase 2 trial, which were presented at the American Association for Cancer Research (“AACR”) Special Conference on ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06896188

NCT06896188 | 9-ING-41 Combined With Retifanlimab, ... This is a study of the combination of 9 ING-41 (elraglusib) and retifanlimab plus mFOLFIRINOX in patients with pancreatic cancer without prior systemic therapy ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2599

A phase 1/2 study of retifanlimab (INCMGA00012, Anti–PD ... This open-label, nonrandomized phase 1/2 study (NCT04370704) aims to determine optimal doses and preliminary safety and efficacy for the monoclonal antibody ...

4. oncodaily.com oncodaily.com/drugs/zynyz-retifanlimab-dlwr-patient-version

Zynyz (Retifanlimab-dlwr): What Patients Should Know in ... In the POD1UM-202 trial for patients with SCAC who had already tried platinum chemotherapy, Zynyz alone had a 14% response rate with a median ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10982862/

A phase II study of retifanlimab, a humanized anti-PD-1 ... Retifanlimab demonstrates clinical efficacy in PD-1 inhibitor-responsive tumors, including melanoma, UC, NSCLC, and RCC.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04116073?cond=PANCREATIC+CANCER&aggFilters=status%3A

INCMGA00012 in Patients With Previously Treated Unresectable ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2023.41.16_suppl.2599

A phase 1/2 study of retifanlimab (INCMGA00012, Anti–PD ... Here we report initial safety and efficacy results. Methods: Study consists of 4 parts in phase 1 and 2 expansion cohorts in phase 2. In phase 1, parts 1 and 2 ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT402054

A phase 1/2 study of retifanlimab (INCMGA00012, Anti–PD ... Here we report initial safety and efficacy results. Methods: Study consists of 4 parts in phase 1 and 2 expansion cohorts in phase 2. In phase 1, parts 1 and 2 ...

9. onclive.com onclive.com/view/retifanlimab-displaces-chemo-alone-as-the-frontline-standard-of-care-in-scac

Retifanlimab Displaces Chemo Alone as the Frontline ... Retifanlimab is the first and only immunotherapy agent to receive an indication for the frontline treatment of patients with advanced SCAC.