Lu-DOTA-TATE + Chemotherapy + Immunotherapy for Small Cell Lung Cancer

Recruiting at 21 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Antibacterials, Antifungals, Antivirals, others

Disqualifiers: Autoimmune diseases, Severe infections, ECG abnormalities, others

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

Compensation: Varies

Number of Visits: 1

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to establish a safe and well tolerated dose of \[177Lu\]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in this setting and to assess preliminary efficacy of this combination treatment versus the combination of carboplatin, etoposide, and atezolizumab.The study will be essential to assess a new potential therapeutic option in participants with this aggressive cancer type.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have severe infections requiring treatment or are on certain immune therapies, you may need to stop those before joining.

What data supports the effectiveness of the drug Lu-DOTA-TATE for treating small cell lung cancer?

Research shows that Lu-DOTA-TATE, a radiolabeled somatostatin analog, has been effective in treating various neuroendocrine tumors, including small cell lung cancer, by targeting specific receptors on tumor cells. It has shown promising results in tumor regression and survival in animal models and has been used successfully in patients with other types of neuroendocrine tumors. ^{1 2 3 4 5}

Is Lu-DOTA-TATE safe for use in humans?

Lu-DOTA-TATE has been used as a treatment for neuroendocrine tumors, and studies have focused on its early efficacy and toxicity, indicating it has been evaluated for safety in humans. However, specific safety data for its use in combination with chemotherapy and immunotherapy for small cell lung cancer is not provided in the available research. ^{3 6 7 8 9}

What makes the Lu-DOTA-TATE + Chemotherapy + Immunotherapy treatment unique for small cell lung cancer?

This treatment is unique because it combines a radiopharmaceutical, [177Lu]Lu-DOTA-TATE, which targets somatostatin receptors on cancer cells, with chemotherapy and immunotherapy, potentially enhancing the overall effectiveness against small cell lung cancer. The use of [177Lu]Lu-DOTA-TATE is novel in this context, as it has primarily been used for neuroendocrine tumors, and its combination with other therapies could offer a new approach for this aggressive cancer type. ^{2 3 8 10 11}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed ES-SCLC who haven't had treatment yet. They need a positive PET scan showing SSTR and at least one measurable tumor lesion. People can't join if they have brain metastasis, autoimmune diseases, severe infections, recent major surgery, ECG abnormalities that pose risks, known drug hypersensitivity or are in another clinical study.

Inclusion Criteria

I have at least one tumor that can be measured on a CT scan.

I am 18 years old or older.

I can provide a sample of my tumor for further testing.

Exclusion Criteria

You have an ongoing autoimmune disease or a history of autoimmune disease that could come back.

I do not have severe infections needing strong antibiotics or antivirals recently.

Concurrent participation in another therapeutic clinical study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment - Induction

Participants receive [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide, and atezolizumab

6 weeks

Weekly visits (in-person)

Treatment - Maintenance

Participants continue treatment with [177Lu]Lu-DOTA-TATE and atezolizumab

Variable, based on response

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Regular visits (in-person)

Treatment Details

Interventions

• [177Lu]Lu-DOTA-TATE
• Carboplatin
• Etoposide
• Tislelizumab

Trial Overview The study tests the safety of [177Lu]Lu-DOTA-TATE combined with carboplatin, etoposide, and tislelizumab as initial treatment for ES-SCLC. It also looks at using tislelizumab alone as ongoing maintenance therapy after the first treatments.

Participant Groups

Group I: Phase II Experimental arm Experimental Treatment 4 Interventions

\[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)

Group II: Phase II Control arm Experimental Treatment 4 Interventions

Carboplatin, etoposide and atezolizumab alone (control arm)

Group III: Dose Level 4 (DL4) Experimental Treatment 5 Interventions

Dose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.

Group IV: Dose Level 3b (DL3b) Experimental Treatment 5 Interventions

Dose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.

Group V: Dose Level 3a (DL3a) Experimental Treatment 5 Interventions

Dose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.

Group VI: Dose Level 2b (DL2b) Experimental Treatment 5 Interventions

Dose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.

Group VII: Dose Level 2a (DL2a) Experimental Treatment 5 Interventions

Dose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.

Group VIII: Dose Level 1 (DL1) Experimental Treatment 5 Interventions

Dose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.

[177Lu]Lu-DOTA-TATE is already approved in European Union, United States for the following indications:

Approved in European Union as Lutathera for:

• Unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults

Approved in United States as Lutathera for:

• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults
• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in children aged 12 years and older

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

177Lu-octreotate therapy showed potential effectiveness in treating paragangliomas and meningiomas, with some patients experiencing tumor regression or stable disease, although response rates were lower than in gastroenteropancreatic neuroendocrine tumors.

The treatment did not demonstrate any antitumor effects in patients with small cell lung carcinoma or melanoma, highlighting the need for further studies to confirm these findings due to the small patient sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. van Essen, M., Krenning, EP., Kooij, PP., et al.[2013]

Salvage treatment with [177Lu-DOTA,Tyr3]octreotate is effective and safe for patients with progressive bronchial neuroendocrine tumors (NET) or gastroenteropancreatic NET (GEP-NET), showing a median overall survival of 80.8 months after initial treatment.

The treatment resulted in low rates of severe side effects, with only 6.6% and 7.7% of patients experiencing grade III/IV bone marrow toxicity after re-treatment and re-re-treatment, respectively, and no cases of severe kidney toxicity were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. van der Zwan, WA., Brabander, T., Kam, BLR., et al.[2020]

(177)Lu-DOTA-Tyr(3)-octreotate demonstrated the highest tumor uptake in small cell lung cancer (SCLC) models, indicating its potential as an effective therapeutic option compared to other radiopharmaceuticals.

(111)In-DTPA-octreotide showed better tumor localization than (99m)Tc-depreotide, suggesting that (111)In-DTPA-octreotide may be more effective for detecting SCLC due to its higher tumor-to-normal tissue activity concentration ratios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model. Schmitt, A., Bernhardt, P., Nilsson, O., et al.[2019]

In a study of 33 patients with progressive gastroenteropancreatic or bronchial neuroendocrine tumors, additional therapy with (177)Lu-octreotate resulted in renewed tumor regression in 8 patients, demonstrating its potential as a salvage treatment after initial therapy.

The treatment was generally well-tolerated, with no serious delayed adverse events reported, indicating that (177)Lu-octreotate is a safe option for patients who have experienced disease progression after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. van Essen, M., Krenning, EP., Kam, BL., et al.[2022]

The somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate shows a nine-fold higher affinity for somatostatin receptor subtype 2 compared to [111In-DTPA0]octreotide, suggesting it may be more effective for targeting tumors in patients with somatostatin receptor-positive tumors.

In a study involving six patients, [177Lu-octreotate] demonstrated significantly higher tumor uptake (three- to fourfold) compared to [111In-octreotide], while also reducing kidney radiation exposure by 47% when amino acids were co-infused, indicating a safer and potentially more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Kwekkeboom, DJ., Bakker, WH., Kooij, PP., et al.[2022]

In a study of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

A study of 32 administrations of [177Lu]Lu-DOTA-TATE showed that using lead aprons significantly reduced radiation exposure for medical staff, with reductions of up to 71% for physicians and 68% for nurses.

The average radiation dose measured was consistent across different monitoring methods, indicating that with proper safety measures, administering [177Lu]Lu-DOTA-TATE can be done safely, although regular monitoring is essential to stay within annual dose limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. Riveira-Martin, M., Struelens, L., Muñoz Iglesias, J., et al.[2023]

The study developed and validated a high-performance liquid chromatography (HPLC) method for quality control of the radiopeptide [177Lu]Lu-DOTA-TATE, ensuring its radiochemical purity meets therapeutic standards (95-105% of label claim).

The HPLC method demonstrated accuracy, precision, and sensitivity, making it suitable for clinical samples, which is crucial for the safe and effective use of [177Lu]Lu-DOTA-TATE in treating neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations. van Andel, L., Aalbersberg, EA., Geluk-Jonker, MM., et al.[2021]

The development of a single vial kit for (177) Lu-DOTATATE allows for safe and efficient preparation of this radiopharmaceutical in hospital settings, making it more accessible for treating patients with inoperable neuroendocrine tumors.

Preclinical studies showed that (177) Lu-DOTATATE is rapidly cleared from the body through the kidneys, indicating a favorable biodistribution profile that supports its use in peptide receptor radionuclide therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. Mukherjee, A., Lohar, S., Dash, A., et al.[2019]

Lutetium-177 labeled radiopharmaceuticals, specifically 177Lu-EDTMP and 177Lu-DOTA-TATE, have shown promising efficacy in treating bone pain from metastatic cancer and neuroendocrine tumors, with no serious adverse effects reported even in patients with renal disease.

In a study involving 13 patients, 177Lu-EDTMP demonstrated high and rapid uptake in bone metastases, while 177Lu-DOTA-TATE resulted in partial remissions in 4 out of 5 patients, indicating effective therapeutic responses without significant renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay. Balter, H., Victoria, T., Mariella, T., et al.[2019]

A ready-to-use formulation of 177Lu-DOTA-TATE was developed for treating neuroendocrine tumors, achieving over 90% radiolabeling yields and maintaining safety for human use for more than a week with high radiochemical purity.

The optimized production process allows for bulk scale preparation, ensuring consistent availability of this effective radiopharmaceutical for patient treatment across various nuclear medicine centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. Mathur, A., Prashant, V., Sakhare, N., et al.[2018]

References

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

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. [2013]

2. Germany pubmed.ncbi.nlm.nih.gov

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. [2020]

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

Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model. [2019]

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

Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. [2022]

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

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. [2019]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay. [2019]

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

Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. [2018]