Cinrebafusp Alfa in Combination With Ramucirumab and Paclitaxel in HER2-High Gastric or GEJ Adenocarcinoma and in Combination With Tucatinib in HER2-Low Gastric or GEJ Andenocarinoma

Recruiting at 4 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

80 Participants Needed

Trial Summary

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.

What safety data exists for treatments like nab-paclitaxel (Abraxane) and other related drugs?

Nab-paclitaxel (Abraxane) is generally considered to have less toxicity compared to traditional paclitaxel (Taxol), and it is FDA approved for several cancers. However, taxane-derived drugs, including nab-paclitaxel, can cause neurotoxicity (nerve damage), which is a known side effect. ^{1 2 3 4 5}

How is the drug Cinrebafusp Alfa, Paclitaxel, Ramucirumab, Tucatinib different from other treatments?

This treatment combines multiple drugs, including nab-paclitaxel, which is a unique formulation of paclitaxel that doesn't require premedication and is suitable for patients with alcohol intolerance. Nab-paclitaxel has shown effectiveness in various cancers and is well-tolerated, making it a novel option compared to traditional solvent-based paclitaxel. ^{1 3 6 7 8}

What is the purpose of this trial?

This trial tests a new treatment called cinrebafusp alfa combined with other cancer drugs in patients with stomach or GEJ cancer. It targets a protein called HER2 to help the immune system destroy cancer cells.

Research Team

Gordon Otto, MD, PhD

Principal Investigator

Pieris Pharmaceuticals, Inc.

Eligibility Criteria

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

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

Treatment Details

Interventions

• Cinrebafusp Alfa
• Paclitaxel
• Ramucirumab
• Tucatinib

Participant Groups

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+

Findings from Research

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]

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-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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. [2021]

2. England 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. [2020]

3. United States 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). [2022]

4. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical experience of nab-Paclitaxel treatment in 31 patients with breast cancer]. [2015]

7. England pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of breast cancer: an update across treatment settings. [2020]

8. England pubmed.ncbi.nlm.nih.gov

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