INCMGA00012 + Pelareorep for Triple Negative Breast Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mridula George, MD

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, CNS metastases, 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

Compensation: Varies

Number of Visits: 34

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, INCMGA00012 and pelareorep, to determine their safety and effectiveness in treating triple negative breast cancer that has metastasized. INCMGA00012 is a medicine that helps the immune system attack cancer cells, while pelareorep is a virus that naturally targets and breaks down cancer cells. Women who have received 1-2 prior treatments for metastatic triple negative breast cancer and have confirmed cancer through testing are suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on a stable anticoagulant regimen, you can continue it during the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of the drugs INCMGA00012 and pelareorep was well-tolerated in past studies. Participants in these trials reported no safety concerns. This suggests that using both treatments together appears safe. Participants experienced no major issues, indicating the treatment is potentially safe for those considering joining similar clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for triple-negative breast cancer, which often include chemotherapy, INCMGA00012 (also known as retifanlimab) and Pelareorep work in a novel way. INCMGA00012 is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. Pelareorep is a type of oncolytic virus that selectively infects and kills cancer cells while also stimulating the body's immune response. Researchers are excited about these treatments because they offer a two-pronged attack by both directly targeting cancer cells and boosting the body's natural defenses against the tumor, which could lead to improved outcomes for patients.

What evidence suggests that this treatment might be an effective treatment for triple negative breast cancer?

This trial will study the combination of INCMGA00012 and pelareorep for treating triple-negative breast cancer. Studies have shown that combining INCMGA00012, a monoclonal antibody that helps the immune system target cancer cells by blocking a specific pathway, with pelareorep, a virus that naturally breaks down cancer cells, could be effective. Early research suggests that these treatments together might slow cancer growth and spread. Initial findings have been positive, indicating potential benefits for patients with advanced triple-negative breast cancer. Researchers continue to study this combination treatment to understand its full effects. ^{1 2 5 6 7}

Who Is on the Research Team?

Mridula A George

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

This trial is for women with metastatic triple negative breast cancer who've had 1-2 prior systemic therapies. They must not be pregnant, have certain blood and organ function levels within set limits, and agree to use two forms of contraception if of childbearing potential. Exclusions include lung disease history, more than three prior treatments in the metastatic setting, known severe allergies to study drugs or components, recent serious cardiovascular events, untreated brain metastases among others.

Inclusion Criteria

Your lactate dehydrogenase (LDH) level is below twice the upper limit of normal.

Your hemoglobin level is 9.0 grams per deciliter or higher.

My triple negative breast cancer returned as metastatic within 6 months after completing initial treatment.

Exclusion Criteria

I haven't had vaccines like the flu shot within the last 4 weeks.

I have had cancer before, but it was either a non-dangerous skin cancer, a localized cancer that did not spread, or any cancer that I've been free of for over a year.

I do not have active brain cancer that needs treatment, or I have small, symptom-free brain lesions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pelareorep IV on days 1, 2, 15, and 16, and retifanlimab IV on day 3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

4 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 and 90 days, then every 6 months for up to 2 years.

Up to 2 years

Follow-up visits at 30 and 90 days, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• INCMGA00012
• Pelareorep

Trial Overview The IRENE Study is testing INCMGA00012 (a monoclonal antibody targeting PD-1) combined with pelareorep (a naturally occurring virus that may destroy cancer cells) against metastatic triple negative breast cancer. The phase 2 trial aims to assess safety and effectiveness while also requiring quality-of-life assessments through questionnaires.

How Is the Trial Designed?

Group I: Treatment (pelareorep, retifanlimab) Experimental Treatment 4 Interventions

Patients receive pelareorep IV over 60 minutes on days 1, 2, 15, and 16. Patients also receive INCMGA00012 IV over 60 minutes on day 3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Mridula George, MD

Lead Sponsor

Trials

3

Recruited

60+

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

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

Oncolytics Biotech

Industry Sponsor

Trials

21

Recruited

1,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In the IMpassion131 trial involving 651 patients with advanced triple-negative breast cancer, adding atezolizumab to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS) compared to paclitaxel alone, indicating that this combination may not provide the expected benefits in treatment outcomes.

While the addition of atezolizumab showed a higher unconfirmed overall response rate and longer duration of response in the PD-L1-positive population, the overall survival results were similar between the two treatment groups, suggesting that the combination therapy does not significantly enhance long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Miles, D., Gligorov, J., André, F., et al.[2021]

Pembrolizumab, when combined with chemotherapy, significantly improves pathological complete response (pCR) and event-free survival (EFS) in patients with high-risk, early-stage triple-negative breast cancer, as shown in the KEYNOTE-522 trial with 123 EFS events in the pembrolizumab group compared to 93 in the control group.

Despite 44% of patients experiencing immune-related adverse reactions, the benefits of pembrolizumab, including a 7.5% absolute improvement in pCR rates, support its use as an effective neoadjuvant and adjuvant treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. Shah, M., Osgood, CL., Amatya, AK., et al.[2023]

In a study involving 614 patients with advanced triple-negative breast cancer, the SP142 assay identified 46.4% of patients as PD-L1 positive, while the SP263 and 22C3 assays identified significantly higher rates of 74.9% and 73.1%, respectively, indicating that different assays can yield varying results in PD-L1 positivity.

The clinical efficacy of atezolizumab plus nab-paclitaxel was primarily observed in patients who were double-positive for SP142 and either SP263 or 22C3, suggesting that the SP142 assay may be more predictive of treatment benefit compared to the other assays, despite the latter identifying more patients as PD-L1 positive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer. Rugo, HS., Loi, S., Adams, S., et al.[2023]

In a phase II trial involving 50 patients with early triple-negative breast cancer, 66% achieved a pathological complete response (pCR) after treatment with nab-paclitaxel and pembrolizumab, indicating a promising efficacy of this combination therapy.

The treatment was associated with manageable side effects, with fatigue, peripheral sensory neuropathy, and neutropenia being the most common adverse events, suggesting that this regimen could be a viable alternative to platinum-based chemotherapy for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041). Fasching, PA., Hein, A., Kolberg, HC., et al.[2023]

Sacituzumab govitecan (IMMU-132) has been shown to prolong progression-free survival in patients with advanced triple-negative breast cancer, indicating its efficacy as a treatment option.

The treatment is well tolerated, resulting in fewer and more manageable side effects compared to traditional irinotecan, suggesting a safer profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An ADC for Triple-Negative Breast Cancer. [2018]

In a phase 3 trial involving 622 patients with metastatic triple-negative breast cancer, pembrolizumab did not significantly improve overall survival compared to standard chemotherapy, with median survival times of 9.9 months for pembrolizumab and 10.8 months for chemotherapy.

Pembrolizumab showed a manageable safety profile, with fewer severe treatment-related adverse events compared to chemotherapy, suggesting it may be safer for some patients despite not demonstrating superior efficacy overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Winer, EP., Lipatov, O., Im, SA., et al.[2021]

In the phase III KEYNOTE-522 trial, pembrolizumab combined with chemotherapy showed increased effectiveness as a neoadjuvant treatment for triple-negative breast cancer, leading to a higher rate of pathologic complete response compared to chemotherapy alone.

This benefit was observed regardless of the PD-L1 expression levels in patients, suggesting that pembrolizumab may be a broadly effective option for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pembrolizumab Takes on TNBC. [2020]

Pembrolizumab, an anti-PD-1 monoclonal antibody, has been shown to significantly improve treatment outcomes for high-risk, early-stage triple-negative breast cancer (TNBC) when combined with standard chemotherapy, leading to a marked increase in pathologic complete response rates and 3-year event-free survival, as demonstrated in the KEYNOTE-522 trial.

The FDA approved pembrolizumab in July 2021, marking a significant shift in the treatment approach for TNBC, which has historically been challenging due to its aggressive nature and limited targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer: Spotlight on Pembrolizumab. Bagegni, NA., Davis, AA., Clifton, KK., et al.[2023]

Citations

1. cancertherapyadvisor.com cancertherapyadvisor.com/news/retifanlimab-pelareorep-metastatic-triple-negative-breast-cancer/

Retifanlimab and Pelareorep in Metastatic Triple-Negative ... Description: Researchers are conducting a phase 2 study to evaluate the safety and efficacy of retifanlimab (INCMGA00012) and pelareorep for ...

2. oncolyticsbiotech.com oncolyticsbiotech.com/press_releases/oncolytics-biotech-presents-positive-interim-safety-update-from-phase-2-triple-negative-breast-cancer-trial-at-the-2021-san-antonio-breast-cancer-symposium/

Oncolytics Biotech® Presents Positive Interim Safety ... The IRENE (INCMGA00012 and the oncolytic virus pelareorep in metastatic triple-negative breast cancer) study is a single-arm, open-label ...

3. withpower.com withpower.com/trial/phase-3-breast-neoplasms-6-2020-56ec5

INCMGA00012 + Pelareorep for Triple Negative Breast ... This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012 and pelareorep and to see how well they work in treating ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04445844

NCT04445844 | INCMGA00012 and Pelareorep for the ... This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012 and pelareorep and to see how well they work in treating ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04445844/incmga00012-and-pelareorep-for-the-treatment-of-metastatic-triple-negative-breast-cancer-irene-study?activelyRecruiting=false&page=84&id=25005&slug=carcinoma

INCMGA00012 and Pelareorep for the Treatment of ... This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012 and pelareorep and to see how well they work ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT04445844

INCMGA00012 and Pelareorep for the Treatment of ... P2, N=25; IRENE (NCT04445844); "Safety data from the trial show that the combination has been well-tolerated, as no safety concerns have been noted in any ...

7. prnewswire.com prnewswire.com/news-releases/oncolytics-biotech-presents-positive-interim-safety-update-from-phase-2-triple-negative-breast-cancer-trial-at-the-2021-san-antonio-breast-cancer-symposium-301441942.html

Oncolytics Biotech® Presents Positive Interim Safety ... No safety concerns have been noted in any trial participants. - Trial builds on prior clinical data demonstrating pelareorep's ability to ...