Cinrebafusp Alfa Combinations for Gastric Cancer

Not currently recruiting at 5 trial locations

Overseen By M. Jen Tsung

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pieris Pharmaceuticals, Inc.

Must not be taking: NSAIDs, Antiplatelets, Steroids, others

Disqualifiers: CNS metastases, Heart failure, Hypertension, 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: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of a new treatment for stomach cancer and cancer at the gastroesophageal junction. It will explore how well cinrebafusp alfa (an experimental treatment) works with other drugs, depending on whether the cancer is HER2-high or HER2-low. Participants should have this type of cancer and have previously tried at least one other treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like NSAIDs and some anticoagulants need to be adjusted or switched. 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 cinrebafusp alfa, combined with tucatinib, is being tested for safety in people with stomach cancer. This phase 2 study indicates that the treatment appeared safe in earlier tests, but more information is needed to assess how well people tolerate it.

In another study, researchers administered cinrebafusp alfa with ramucirumab and paclitaxel to 5 patients. The treatment was safe and generally well-tolerated, with some side effects that were not severe enough to halt the treatment.

In summary, early results suggest these treatment combinations are generally well-tolerated, but further studies are needed to better understand their safety in a larger group. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cinrebafusp Alfa because it offers a new approach for treating gastric or gastroesophageal junction (GEJ) adenocarcinoma by enhancing the immune system's ability to target cancer cells. Unlike traditional treatments like chemotherapy, Cinrebafusp Alfa is a bispecific antibody designed to direct the immune system to HER2-expressing cancer cells more precisely. In combination with other drugs, such as tucatinib for HER2-low cancers and ramucirumab with paclitaxel for HER2-positive cancers, it aims to deliver a more tailored and potentially more effective attack on tumors. This targeted mechanism provides hope for improved outcomes compared to standard treatments, which often involve broad-spectrum chemotherapy.

What evidence suggests that this trial's treatments could be effective for gastric or gastroesophageal junction adenocarcinoma?

Studies have shown promising results for cinrebafusp alfa in treating stomach cancer and cancer at the junction where the stomach meets the esophagus. In this trial, participants with HER2-low cancer will receive a combination of cinrebafusp alfa and tucatinib, which shows potential by blocking signals that help cancer grow. Participants with HER2-high cancer will receive cinrebafusp alfa combined with ramucirumab and paclitaxel, which has been well tolerated and has shown encouraging results. Ramucirumab cuts off the blood supply to the tumor, while paclitaxel is a chemotherapy drug that kills cancer cells. These combinations are being studied for their ability to effectively target and treat these specific types of cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Gordon Otto, MD, PhD

Principal Investigator

Pieris Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Signed written informed consent obtained prior to performing any study procedure, including screening procedures

Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cinrebafusp alfa in combination with ramucirumab and paclitaxel or tucatinib based on HER2 status

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cinrebafusp Alfa
• Paclitaxel
• Ramucirumab
• Tucatinib

How Is the Trial Designed?

Group I: Cinrebafusp alfa (PRS-343) in combination with tucatinib Experimental Treatment 1 Intervention

Patients aged 18 years or older with HER2 low (IHC 1+ or IHC 2+ without HER2/neu amplification) gastric or GEJ adenocarcinoma who have received at least one prior treatment regimen

Group II: Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel Experimental Treatment 1 Intervention

Patients aged 18 years or older with HER2-positive gastric or GEJ adenocarcinoma who have progressed on prior treatment with a regimen containing a platinum and fluoropyrimidine and a HER2-directed therapy such as trastuzumab and now are candidates for treatment with ramucirumab and paclitaxel

Who Is Running the Clinical Trial?

Pieris Pharmaceuticals, Inc.

Lead Sponsor

Trials

4

Recruited

250+

Published Research Related to This Trial

Atezolizumab, when used with nab-paclitaxel for treating triple negative breast cancer, can cause rare side effects like autoimmune hemolytic anemia, as seen in a case study of a 59-year-old female patient.

The patient's hemolytic anemia was effectively managed with a high-dose prednisone taper, allowing her to continue her cancer treatment without further complications through multiple cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. Younce, CM., Lawton, JM., Patel, DR.[2021]

Nab-paclitaxel (Abraxane(®)) combined with carboplatin has been approved for treating advanced non-small-cell lung cancer (NSCLC) and showed a significantly improved overall response rate compared to traditional solvent-based paclitaxel in a Phase III trial.

Patients receiving nab-paclitaxel experienced fewer side effects such as neutropenia and neuropathy, making it a safer option, although it was associated with more thrombocytopenia and anemia compared to solvent-based paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-paclitaxel for the management of patients with advanced non-small-cell lung cancer. Hirsh, V.[2022]

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

A study analyzing 3,940 cases from the FDA Adverse Event Reporting System found that taxane-related neurotoxicity, particularly peripheral neuropathy, is common, especially among elderly patients and females.

The median time for neurological adverse effects to appear after taxane treatment was 27 days, with a significant portion of cases occurring within the first 30 days, and the study reported a fatality rate of 6.13% and hospitalization rate of 28.63% for these adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021. Zhang, J., Luo, L., Long, E., et al.[2023]

In a phase 3 trial involving 902 patients with metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel showed a median overall survival of 21.0 months compared to 18.7 months with placebo, although this difference was not statistically significant in the overall population.

For patients with PD-L1 immune cell-positive tumors, atezolizumab plus nab-paclitaxel demonstrated a significant overall survival benefit, with a median survival of 25.0 months versus 18.0 months for placebo, highlighting its potential as an important treatment option for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Schmid, P., Rugo, HS., Adams, S., et al.[2020]

Nab-PTX (Abraxane®) was administered to 31 breast cancer patients without any allergic reactions, indicating it is well tolerated, even in those with alcohol intolerance.

Among patients with locally advanced operable breast cancer, higher doses (260 mg/m²) resulted in a better response rate, with 10 out of 13 showing a partial response, suggesting its efficacy in treating advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of nab-Paclitaxel treatment in 31 patients with breast cancer]. Tauchi, Y., Kashiwagi, S., Ishihara, S., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05190445

Study Details | NCT05190445 | Cinrebafusp Alfa in ... This is a multi-center, open-label study of cinrebafusp alfa in combination with clinically established doses of ramucirumab and paclitaxel in patients with ...

2. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/CT122/703188/Abstract-CT122-A-phase-2-multi-center-open-label

A phase 2, multi-center, open-label study of cinrebafusp alfa ... This is a global, open-label, multicenter, two-arm phase 2 trial of cinrebafusp alfa in patients with metastatic gastric or gastroesophageal junction cancer.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00833-X/fulltext

P-53 A phase 2, multi-center, open-label study ... This is a global, open-label, multicenter, two-arm phase 2 trial of cinrebafusp alfa in patients with metastatic gastric or gastroesophageal junction cancer.

4. targetedonc.com targetedonc.com/view/cinrebafusp-alfa-combinations-explored-in-her2-expressing-gastric-cancer

Cinrebafusp Alfa Combinations Explored in HER2- ... A study of cinrebafusp alfa is underway to evaluate its safety and efficacy in combination with other therapies in patients with gastric or ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11386020/

HER2-low gastric cancer: is the subgroup targetable? - PMC The ToGA trial found that trastuzumab, a monoclonal antibody targeting HER2, significantly improved overall survival (OS) when combined with chemotherapy for ...

6. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT154/725485/Abstract-CT154-Combination-of-cinrebafusp-alfa

Abstract CT154: Combination of cinrebafusp alfa with ... The combination of cinrebafusp alfa with ramucirumab and paclitaxel was safe and tolerated in the 5 patients treated.