Radioactive Drugs for Breast Cancer

Recruiting at 6 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Low blood counts, QTcF ≥ 470 msec, others

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

Compensation: Varies

Number of Visits: 1

124 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug [177Lu]Lu-NNS309 for breast cancer?

Research on similar drugs, like trastuzumab labeled with 177Lu, shows increased effectiveness in breast cancer cells, suggesting that [177Lu]Lu-NNS309 might also be effective. Additionally, 177Lu has been used successfully in other cancer treatments, indicating its potential as a powerful cancer-fighting agent. ^{1 2 3 4 5}

Is the treatment with radioactive drugs like [177Lu]Lu-NNS309 generally safe for humans?

Research on similar radioactive drugs, like 177Lu-DOTATATE, shows they are generally considered safe, with studies focusing on their effects on organs and blood. However, they can cause some kidney and blood-related side effects, which are monitored during treatment. ^{1 2 3 6 7}

What makes the drug [177Lu]Lu-NNS309 unique for treating breast cancer?

The drug [177Lu]Lu-NNS309 is unique because it uses a radioactive isotope, Lutetium-177, which emits beta particles to target and destroy cancer cells, potentially offering a more direct and potent treatment compared to traditional therapies. This approach is similar to other 177Lu-based treatments that have shown effectiveness in targeting specific cancer cells, such as HER2-positive breast cancer, by combining the radioactive element with antibodies that specifically bind to cancer cell markers. ^{2 3 8 9 10}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-NNS309 and the safety and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer (BC), triple negative breast cancer (TNBC) and colorectal cancer (CRC).

Eligibility Criteria

This trial is for adults with certain advanced cancers (pancreatic, lung, breast, colorectal) that can't be removed by surgery or have spread. They should have tried other treatments unless they couldn't due to health reasons. Their cancer must also show up on a special scan using [68Ga]Ga-NNS309.

Inclusion Criteria

My breast cancer is advanced, cannot be surgically removed, and has worsened after at least 2 treatments.

I have advanced pancreatic cancer and have had chemotherapy, unless I was unable to receive it.

My advanced lung cancer has no treatable gene changes and I've had chemo and immunotherapy, or it has treatable gene changes and I've had targeted therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Patients are initially imaged with a [68Ga]Ga-NNS309 PET/CT or PET/MRI scan to evaluate eligibility for [177Lu]Lu-NNS309 treatment

Up to 3 days

1 visit (in-person)

Dose Escalation

Different doses of [177Lu]Lu-NNS309 are tested to identify recommended dose(s) for further evaluation

Up to 24 weeks

Dose Expansion

Safety and preliminary efficacy of [177Lu]Lu-NNS309 at the recommended dose(s) are examined

Up to 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• [177Lu]Lu-NNS309
• [68Ga]Ga-NNS309

Trial Overview [177Lu]Lu-NNS309 and [68Ga]Ga-NNS309 are being tested for safety and effectiveness in treating specific advanced cancers. The study will look at how the body processes these substances and whether they help in detecting or fighting cancer.

Participant Groups

Group I: Arm 1 Experimental Treatment 2 Interventions

Patients will receive \[68Ga\]Ga-NNS309, and if eligible, \[177Lu\]Lu-NNS309

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

The maximum tolerated dose (MTD) of [177Lu]Lu-LNC1003 for treating metastatic castration-resistant prostate cancer was determined to be 1.85 GBq, with doses of 1.11 and 1.85 GBq per cycle being well tolerated by patients.

The treatment showed promising efficacy, with a PSA decline observed in a significant number of patients, particularly at the 1.85 GBq dose level, indicating potential therapeutic benefits for patients with bone and lymph node metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer. Zang, J., Wang, G., Zhao, T., et al.[2023]

NCA-LuTATE, a radiolabeled peptide used for treating neuroendocrine tumors, has been administered safely in 39 injections across 13 patients, showing an acceptable radiation safety profile with an average kidney dose of 3.1 Gy per treatment cycle.

The study found that the clearance of NCA-LuTATE is influenced by the patient's kidney function, which is important for estimating radiation doses, and it produces less radioactive waste compared to traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. Bailey, DL., Hennessy, TM., Willowson, KP., et al.[2020]

The study developed a new radiopharmaceutical by labeling trastuzumab with (177)Lu, which demonstrated high radiochemical purity (91%) and stability in both PBS buffer and blood serum for up to 96 hours.

Trastuzumab-(177)Lu showed significantly increased cytotoxicity, with a five-fold increase in toxicity against HER2-positive SKBr3 breast cancer cells compared to unlabeled trastuzumab, indicating its potential as an effective treatment for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of trastuzumab labeled 177Lu on MCF7 and SKBr3 cell lines. Rasaneh, S., Rajabi, H., Hossein Babaei, M., et al.[2015]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

The novel radiopharmaceutical agent 177Lu-DOTA-DG was successfully synthesized with a high radiochemical yield and demonstrated excellent stability in human serum for up to 120 hours, indicating its potential for safe use in cancer imaging and therapy.

In preclinical studies, 177Lu-DOTA-DG caused significantly more DNA damage in cancer cells compared to untreated cells, suggesting its efficacy as a targeted treatment for cancer tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. Zhang, J., Wang, Z., Liu, H., et al.[2019]

In a study of 468 patients with metastatic neuroendocrine tumors (NETs) treated with 177Lu-DOTATATE PRRT, significant improvements were observed in symptoms and biochemical markers, with a median follow-up of 46 months showing a progression-free survival (PFS) rate of 71.1% and overall survival (OS) rate of 79.4% at 7 years.

The treatment was well-tolerated, with minimal toxicity reported; only 1.7% of patients experienced Grade 1 hematological toxicity, and nephrotoxicity was also low, indicating that 177Lu-DOTATATE PRRT is both effective and safe for long-term use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of indigenous 177Lu-DOTATATE PRRT in patients with Metastatic Advanced Neuroendocrine Tumours: a single institutional observation in a large tertiary care setting. Sitani, K., Parghane, RV., Talole, S., et al.[2022]

Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is a safe and effective treatment for patients with inoperable or metastatic neuroendocrine neoplasia (NEN), showing a clinical response of regressive disease in 47.6% of cases.

The study found no severe renal or hematological toxicity in 30 patients treated with Lu-DOTATATE, suggesting that while hematological parameters may influence survival, the treatment itself is well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. Löser, A., Schwarzenböck, SM., Heuschkel, M., et al.[2018]

The 177Lu-labeled immunoconjugate 177Lu-CC49 effectively delayed the growth of established human colon carcinomas in mice, demonstrating its potential as a therapeutic option for cancer treatment.

While higher doses of 177Lu-CC49 showed toxicity, a fractionated dose of 750 microCi was well tolerated and successfully eliminated tumors in 90% of treated mice, indicating a promising therapeutic window for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate. Schlom, J., Siler, K., Milenic, DE., et al.[2013]

The combination of Lutetium-177 with trastuzumab effectively targets HER2-positive breast cancer cells, demonstrating a maximum binding of 10.7% to these cells, which confirms its specificity for the HER2 receptor.

The radioimmunoconjugate induces dose-dependent cellular toxicity primarily through apoptosis, significantly affecting the cell cycle by increasing G2/M phase arrest, which enhances the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dependent cell cycle arrest and apoptosis in HER2 breast cancer cells by177Lu-CHX-A"-DTPA-Trastuzumab. Sharma, R., Kameswaran, M., Pandey, U., et al.[2022]

The radionuclide lutetium-177 (177Lu) shows promise for palliative treatment of pain in bone metastases, with 177Lu-MDP and 177Lu-EDTMP demonstrating effective therapeutic results and rapid dose accumulation compared to other treatments.

Both 177Lu-MDP and 177Lu-EDTMP have high radiochemical stability (about 99%) and target bone tissue effectively, while minimizing exposure to healthy organs like the kidneys and liver, making them safer options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative studies on the potential use of 177Lu-based radiopharmaceuticals for the palliative therapy of bone metastases. Zakaly, HMH., Mostafa, MYA., Deryabina, D., et al.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer. [2023]

2. Iran pubmed.ncbi.nlm.nih.gov

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Toxicity of trastuzumab labeled 177Lu on MCF7 and SKBr3 cell lines. [2015]

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

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Long-term outcome of indigenous 177Lu-DOTATATE PRRT in patients with Metastatic Advanced Neuroendocrine Tumours: a single institutional observation in a large tertiary care setting. [2022]

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

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. [2018]

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

Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate. [2013]

9. India pubmed.ncbi.nlm.nih.gov

Dose-dependent cell cycle arrest and apoptosis in HER2 breast cancer cells by177Lu-CHX-A"-DTPA-Trastuzumab. [2022]

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

Comparative studies on the potential use of 177Lu-based radiopharmaceuticals for the palliative therapy of bone metastases. [2020]