NT-112 for Solid Tumors

Recruiting at 25 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Neogene Therapeutics, Inc.

Must not be taking: Immunosuppressants, Systemic steroids

Disqualifiers: CNS malignancy, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any systemic therapy (treatment affecting the whole body) at least 2 weeks before joining. If you're on such medications, you may need to stop them before participating.

What data supports the effectiveness of the drug NT-112 for solid tumors?

Research shows that docetaxel, a component of NT-112, has been effective in improving survival in patients with non-small-cell lung cancer and has shown good clinical response in breast cancer when combined with other drugs. This suggests potential effectiveness of NT-112 for solid tumors. ^{1 2 3 4 5}

How is the treatment NT-112 different from other treatments for solid tumors?

The treatment NT-112 is unique because it involves the use of tumor-infiltrating lymphocytes (TILs), which are the patient's own immune cells extracted from the tumor environment to fight cancer cells, offering a personalized immunotherapy approach for solid tumors. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial tests NT-112, a personalized immune cell treatment, in patients with advanced cancers that have a specific genetic mutation. The treatment boosts the patient's immune cells to target and kill cancer cells. This highly personalized cancer therapy involves giving the patient immune cells that directly attack cancer.

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors like lung, colorectal, pancreatic or endometrial cancer that can't be surgically removed and have worsened despite treatment. Participants must have a specific genetic feature (KRAS G12D mutation) and a certain immune system marker (HLA-C*08:02). They should be relatively well-functioning (ECOG status of 0-1).

Inclusion Criteria

I have been diagnosed with a solid tumor cancer such as lung, colorectal, pancreatic, or endometrial cancer.

My cancer is advanced and cannot be surgically removed, and I've tried at least one standard treatment.

My cancer is advanced and cannot be surgically removed, and I've tried at least one standard treatment.

Exclusion Criteria

I have had cell, gene, or organ transplant therapy before.

I have an active brain cancer diagnosis.

Any form of primary immunodeficiency

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NT-112, an autologous T-cell therapy product, with dose escalation to determine safety and preliminary anti-tumor activity

4 weeks

1 visit (in-person) for infusion

Follow-up

Participants are monitored for safety, including dose-limiting toxicities and adverse events

28 days

Regular monitoring visits

Long-term follow-up

Participants are monitored for overall survival and long-term safety

Up to 24 months

Treatment Details

Interventions

• NT-112

Trial Overview The study tests NT-112, which are T cells from the patient's own body engineered to target cancer cells with the KRAS G12D mutation. It's an early-phase trial to see how safe it is and how well it works against these tough-to-treat cancers.

Participant Groups

Group I: NT-112 Experimental Treatment 1 Intervention

Dose Escalation of NT-112.

Who Is Running the Clinical Trial?

Neogene Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

190+

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Neoadjuvant chemotherapy with epirubicin and docetaxel showed a clinical response in 33 out of 45 breast cancer patients, with a pathological complete response rate of 10%, indicating its effectiveness as a treatment option for large tumors.

The treatment resulted in a 5-year disease-free survival rate of 60.7% and an overall survival rate of 91.8%, suggesting a favorable long-term outcome for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant epirubicin/docetaxel (ET) concomitant chemotherapy for primary breast cancer with tumor diameter >=3.1 cm: results of the Kyushu ET therapy phase II trial. Nishimura, R., Rai, Y., Matsuo, F., et al.[2018]

In a phase II trial involving 76 patients with HER2/neu-negative metastatic breast cancer, the combination of docetaxel and bevacizumab showed a promising objective response rate of 51%, with a median overall survival of 26.3 months.

The treatment was generally well tolerated, with manageable side effects, although common grade 3/4 adverse events included neutropenia (33%) and leukopenia/lymphopenia (25%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01). Hurvitz, SA., Allen, HJ., Moroose, RL., et al.[2020]

In a phase I/II trial involving 93 breast cancer patients, two chemotherapy schedules (6 cycles of 3-weekly and 8 cycles of 2-weekly epirubicin/docetaxel) were tested, showing acceptable toxicity and good clinical responses, with complete response rates of 90% for Schedule A and 93% for Schedule B.

Pre-treatment expression of specific genes, particularly those near the 17q12 region, was linked to better clinical responses, suggesting that these biomarkers could help predict how well patients will respond to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer (LABC) on 2-weekly or 3-weekly schedules: NCIC CTG MA.22. Trudeau, ME., Chapman, JA., Guo, B., et al.[2022]

In a study of 104 patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy, treatment with docetaxel significantly prolonged median survival (7.0 months) compared to best supportive care (4.6 months).

The lower dose of docetaxel (75 mg/m²) was particularly effective, showing a median survival of 7.5 months and a 1-year survival rate of 37%, while also demonstrating manageable toxicity levels, making it a safer option compared to the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. Shepherd, FA., Dancey, J., Ramlau, R., et al.[2023]

In a study of 104 patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy, treatment with docetaxel significantly prolonged median survival (7.5 months for 75 mg/m2 docetaxel vs. 4.6 months for best supportive care).

Docetaxel treatment also resulted in a longer time to disease progression (10.6 weeks vs. 6.7 weeks for best supportive care), with a manageable safety profile, particularly at the 75 mg/m2 dose, where the benefits outweighed the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non-Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy. Shepherd, FA., Dancey, J., Ramlau, R., et al.[2023]

Tumor-infiltrating lymphocyte (TIL) therapy, which uses a patient's own immune cells to target and kill cancer cells, has shown promising efficacy in treating advanced solid tumors based on recent clinical studies.

The review discusses important aspects of TIL therapy, including the lymphodepletion regimen and the use of interleukin-2, while also addressing potential toxicities and the challenges in isolating and generating TILs for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges. Zhao, Y., Deng, J., Rao, S., et al.[2022]

The oncolytic herpes simplex virus G47Δ-mIL12 effectively targets and kills triple-negative breast cancer (TNBC) cells while also stimulating the immune system, showing significant reduction in tumor size and metastasis in both early and late stages of cancer in mouse models.

Treatment with G47Δ-mIL12 enhances the activation of immune cells, particularly CD8+ T cells and dendritic cells, leading to improved anti-tumor immunity, indicating its potential as an effective immunotherapy for TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic Herpes Simplex Virus Encoding IL12 Controls Triple-Negative Breast Cancer Growth and Metastasis. Ghouse, SM., Nguyen, HM., Bommareddy, PK., et al.[2020]

Higher levels of tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) are linked to better treatment responses and higher pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC) and luminal tumors, with pre-NAC TIL levels averaging 33.9% in pCR cases compared to 20.3% in those with residual disease.

Post-NAC, TIL levels significantly decreased from 24.1% to 13.0%, and this decrease was associated with high pCR rates; however, high post-NAC TIL levels correlated with worse disease-free survival in HER2-positive breast cancers, indicating that immune responses can have different implications based on breast cancer subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Molecular Subtypes and Stromal Immune Infiltration before and after Treatment in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy. Hamy, AS., Bonsang-Kitzis, H., De Croze, D., et al.[2020]

In a study of 159 patients with triple-negative breast cancer (TNBC), high levels of tumor-infiltrating lymphocytes (TILs) before neoadjuvant chemotherapy were strongly associated with a higher rate of pathological complete response (pCR) and better survival outcomes.

Patients with high TILs had significantly longer disease-free survival (DFS) and overall survival (OS) compared to those with intermediate or low TILs, suggesting that TILs can serve as a valuable biomarker for predicting treatment response and prognosis in TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive and Prognostic Value of Tumor- Infiltrating Lymphocytes for Pathological Response to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer. Mohammed, AA., Mostafa Elsayed, F., Algazar, M., et al.[2022]

In a study of 92 nasopharyngeal carcinoma (NPC) cases, EBV positive tumors had significantly higher levels of tumor-infiltrating lymphocytes (TILs), specifically CD3, CD4, and CD8, compared to EBV negative tumors, suggesting a potential link between EBV status and immune response.

Higher counts of CD8 TILs were associated with better overall survival in NPC patients, particularly in those with PD-L1 co-expression, indicating that the composition of TILs may be crucial for prognosis and highlights the potential for immunotherapy in treating NPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma. Ooft, ML., van Ipenburg, JA., Braunius, WW., et al.[2022]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Neoadjuvant epirubicin/docetaxel (ET) concomitant chemotherapy for primary breast cancer with tumor diameter >=3.1 cm: results of the Kyushu ET therapy phase II trial. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01). [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer (LABC) on 2-weekly or 3-weekly schedules: NCIC CTG MA.22. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non-Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Oncolytic Herpes Simplex Virus Encoding IL12 Controls Triple-Negative Breast Cancer Growth and Metastasis. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Interaction between Molecular Subtypes and Stromal Immune Infiltration before and after Treatment in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy. [2020]

9. Kuwait pubmed.ncbi.nlm.nih.gov

Predictive and Prognostic Value of Tumor- Infiltrating Lymphocytes for Pathological Response to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma. [2022]