NT-112 for Solid Tumors

Recruiting at 29 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called NT-112 for individuals with certain advanced or difficult-to-remove solid tumors, such as lung or colorectal cancer. The study aims to determine if NT-112, which uses altered T cells (a type of immune cell) to target and attack specific cancer mutations, can be effective. The trial consists of two parts: one to establish the correct dose and another to evaluate its efficacy. Individuals with a KRAS G12D mutation, who have not responded to other treatments, might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Previous studies have generally shown that patients tolerate NT-112 well. Some participants experienced side effects, mostly mild to moderate. Reports included tiredness and nausea, common in many cancer treatments. Serious side effects occurred less frequently. As this is an early-stage study, the main goal is to assess the treatment's safety and the body's response. Researchers closely monitor for any negative effects and adjust doses carefully to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for solid tumors, such as chemotherapy or radiation, aim to destroy rapidly dividing cells but can also harm healthy cells. NT-112 is unique because it specifically targets tumor cells with a novel mechanism, potentially reducing damage to healthy tissues. Researchers are excited about NT-112 because it could offer a more precise approach to treating solid tumors, possibly improving effectiveness while minimizing side effects compared to current options.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that NT-112, a specially designed treatment, targets specific genetic changes in some solid tumors. In lab studies, NT-112 shrank tumors in test models. Participants in this trial may receive NT-112, which early results suggest might help control tumors in individuals with specific genetic traits. Lab studies and successful components of the treatment in other cancer cases support this. Another treatment arm in this trial involves AZD0240, which researchers are also studying for its potential effects on solid tumors. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: NT-112 Experimental Treatment 1 Intervention

Part A Dose Escalation and Part B Dose Expansion of NT-112

Group II: AZD0240 Experimental Treatment 1 Intervention

Part A Dose Escalation and Part B Dose Expansion of AZD0240

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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]

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]

Citations

1. onclive.com onclive.com/view/dr-punekar-on-the-evaluation-of-nt-112-in-kras-g12d-advanced-solid-tumors

Dr Punekar on the Evaluation of NT-112 in KRAS G12D+ ... Salman R. Punekar, MD discusses the rationale for evaluating safety and preliminary anti-tumor activity of NT-112 in solid tumors with the KRAS G12D mutation.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e14533

Non-clinical evaluation of NT-112, an autologous T cell ... In vivo, NT-112 T-cells were able to induce tumor clearance in two independent models. Low frequency chromosomal translocation events (<0.1%) ...

3. withpower.com withpower.com/trial/phase-1-adenocarcinoma-1-2024-0d78b

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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06218914

NCT06218914 | Phase 1 Study to Investigate TCRTs KRAS ... This is a Phase 1, open-label, Phase 1, Multi-Center Master Protocol to evaluate the safety and preliminary Anti-Tumor activity of TCR-Engineered T cells ...

5. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/study00160329

An Open-label, Phase I, Multicenter Study to Evaluate ... An Open-label, Phase I, Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor activity of NT 112 in Human Leukocyte Antigen-C08:02 Positive ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2677

An open-label, phase 1, multicenter study to evaluate the ... An open-label, phase 1, multicenter study to evaluate the safety and preliminary anti-tumor activity of NT-112 in human leukocyte ...

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/NT-112-301

Phase 1 Study to Investigate TCRTs KRAS Mutation in ... This is a Phase 1, open-label, Phase 1, Multi-Center Master Protocol to evaluate the safety and preliminary Anti-Tumor activity of TCR-Engineered T cells (KRAS ...