LuMIERE: A Phase 1/2, Multicenter, Open label, Non randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of [177Lu]Lu-FAP-2286 in Participants with an Advanced Solid Tumor

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Dec 2025 → ongoing

Decision date (initial)

2025-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-508995-12-01

ClinicalTrials.gov

NCT04939610

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Others

• To evaluate objective response rate (ORR) (Phase 2 dose expansion)

• To evaluate the safety and tolerability of [177Lu]Lu FAP 2286 and determine the recommended Phase 2 dose (RP2D) in combination with mFOLFIRINOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC (Phase 2 dose escalation for combination therapy)

Secondary objectives 5

1. To evaluate duration of response (DOR) (Phase 2 dose expansion)
2. To evaluate disease control rate (DCR) (Phase 2 dose expansion)
3. To evaluate progression free survival (PFS) (Phase 2 dose expansion)
4. To further evaluate the safety of [177Lu]Lu-FAP-2286 at the RP2D for monotherapy, the RP2D in combination with mFOLFIRINOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC (Phase 2 dose expansion)
5. To evaluate the safety and tolerability of [68Ga]Ga-FAP-2286

Conditions and MedDRA coding

Recurrent or metastatic non-small cell lung cancer (NSCLC)

Regulatory references

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF) prior to any study-specific evaluation.
2. Be ≥ 18 years of age at the time the ICF is signed.
3. Have consented to submission of fresh or archival tumor tissue, if available.
4. Have adequate organ function confirmed by the following laboratory values obtained within the Screening Period prior to administration of [68Ga]Ga-FAP-2286 and prior to first cycle of chemotherapy in the combination groups: a. Bone Marrow Function (independent of transfusion or growth factor support within 21 days prior to planned first administration of [177Lu]Lu-FAP-2286): i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; ii. Platelets > 100 × 109/L; and iii. Hemoglobin ≥ 9 g/dL. b. Hepatic Function: i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × institutional upper limit of normal (ULN); if liver metastases, then ≤ 5 × the institutional ULN; ii. Serum Bilirubin ≤ 1.5 × institutional ULN or if known Gilbert’s syndrome then ≤ 3 × institutional ULN; iii. Serum albumin ≥ 30 g/L (3 g/dL) and iv. INR ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT)≤1.5 x ULN. This applies to participants who are not receiving therapeutic anticoagulation, participants receiving therapeutic anticoagulation should be on a stable dose. c. Renal Function: i. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min using the Cockcroft-Gault formula.
5. Have an Eastern Oncology Group (ECOG) performance status of 0 or 1.
6. Have a life expectancy of ≥ 6 months.
7. Have measurable disease per RECIST v1.1 meeting the following criteria: a. At least 1 lesion of ≥ 10 mm in the longest diameter for a non-lymph node or ≥ 15 mm in the short-axis diameter for a lymph node that is serially measurable according to RECIST v1.1 using conventional CT and/or MRI. • Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation must show subsequent evidence of substantial size increase to be deemed a target lesion.
8. For Phase 2 only: Have cytologically or histologically and radiologically confirmed recurrent or metastatic disease as outlined below: a. Pancreatic Cancer monotherapy group: i. Pancreatic ductal adenocarcinoma (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded) ii. Participants must have progressed after at least 1, but no more than two prior chemotherapy regimens for locally advanced unresectable or metastatic disease. Criteria b through h removed during Protocol amendment 7. i. Pancreatic Cancer combination group (with mFOLFIRINOX) i. Pancreatic ductal adenocarcinoma (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded); ii. Participants have not received prior systemic therapy for metastatic disease. v. Participants must not have received prior taxane therapy either as monotherapy or in combination.
9. For Phase 2 only: Have cytologically or histologically and radiologically confirmed recurrent or metastatic disease as outlined below: j. Non-small cell lung cancer monotherapy group i. Non-small cell lung cancer (adenocarcinoma and squamous eligible; endocrine, neuroendocrine and small cell tumors are excluded) ii. Participants must have progressed after at least 1 but not more than 2 prior systemic regimens including chemotherapy and immunotherapy, if eligible. Participants with NSCLC and targeted therapy treatment options, are eligible for the clinical trial as long as they meet these criteria (progression after 1 or 2 prior therapies). Note: Participants with NSCLC harbouring mutations amenable to targeted therapy treatment are eligible if received targeted therapy as single agent or in combination in 1st or 2nd line of treatment; participants not eligible to receive such therapies in 1 or 2L are also eligible to participate to the study. iii. Participants who have received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and an immune checkpoint inhibitor and developed recurrent or metastatic disease while on or within 12 months of completing therapy are eligible iv. Participants with recurrent disease > 12 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum-doublet regimen and an immune checkpoint (given either together or sequentially to treat the recurrence), are eligible v. Participants must have received platinum-based chemotherapy for advanced or metastatic disease and immune checkpoint inhibitor either together (in the same line of treatment) or sequentially (two different lines of treatment) and then progressed. k. Non small cell lung cancer combination group i. Non-small cell lung cancer (adenocarcinoma and squamous eligible; endocrine, neuroendocrine and small cell tumors are excluded) ii. Participants must have progressed after at least 1 but not more than 2 prior systemic regimens including chemotherapy and immunotherapy, if eligible. Participants with NSCLC and targeted therapy treatment options, are eligible for the clinical trial as long as they meet these criteria (progression after 1 or 2 prior therapies). Note: Participants with NSCLC harbouring mutations amenable to targeted therapy treatment are eligible if received targeted therapy as single agent or in combination in 1st or 2nd line of treatment; participants not eligible to receive such therapies in 1 or 2L are also eligible to participate to the study. iii. Participants who have received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and an immune checkpoint inhibitor and developed recurrent or metastatic disease while on or within 12 months of completing therapy are eligible iv. Participants with recurrent disease > 12 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum-doublet regimen and an immune checkpoint (given either together or sequentially to treat the recurrence), are eligible v. Participants must not have received prior taxane therapy either as monotherapy or in combination.
10. For Phase 2 only: Have cytologically or histologically and radiologically confirmed recurrent or metastatic disease as outlined below: l. Breast cancer monotherapy group i. Hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative • Participant has a histologically and/or cytologically documented diagnosis of HR positive HER2 negative metastatic breast cancer (based on the most recently analyzed tissue sample tested by a local laboratory). • Participants must have progressed on at least one line of hormone-based therapy (either alone or in combination) and at least one, but not more than two lines of chemotherapy (including cytotoxic, targeted and/or anti-drug conjugate therapies) for metastatic disease. ii. HER2 positive • Participant has a histologically and/or cytologically documented diagnosis of HER2 positive metastatic breast cancer (based on the most recently analyzed tissue sample tested by a local laboratory). • Participant must have progressed on at least two lines of HER2 targeted therapy for metastatic disease. iii. Triple negative breast cancer (TNBC) • Participant has a histologically and/or cytologically documented diagnosis of TNBC (based on the most recently analyzed tissue sample tested by a local laboratory). • Participants must have progressed on at least two lines of cytotoxic chemotherapy (including cytotoxic, anti-drug conjugate, targeted therapies and/or IO) for metastatic disease.

Exclusion criteria 15

1. Active malignancy except for the specific cancer under investigation in this study, ie, participant known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment with the following exceptions: a. History of second malignancy that has been successfully treated, with no evidence of active cancer for 3 years prior to enrollment; b. Surgically cured low-risk tumors, such as early-stage cervical or endometrial cancer, any cancer in situ, or non-melanoma skin cancers; and c. Prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
2. Received prior radiopharmaceutical therapy (eg, radium 223 223Ra-dichloride, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617, actinium 225 [225Ac]Ac-PSMA-617, etc.) or prior EBRT to more than 25% of the bone marrow or received any prior EBRT directly to kidney, or received any EBRT within 2 weeks prior to administration of [177Lu]Lu-FAP-2286. • Prior administration of a radiopharmaceutical unless 10 or more half-lives have elapsed before injection/infusion of [68Ga]Ga-FAP-2286 or [177Lu]Lu-FAP-2286.
3. Ongoing adverse effects from anticancer treatment NCI-CTCAE v5.0 (or higher) Grade 1, with the exception for alopecia and vitiligo.
4. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a. Clinically significant and/or uncontrolled cardiac disease such as congestive heart failure requiring treatment (New York Heart Association > Class 2), uncontrolled hypertension, clinically significant arrhythmia, or congenital prolonged QT syndrome; b. Corrected QT interval (Fridericia’s formula) > 450 msec for males or > 470 msec for females at Screening; or c. Acute coronary syndrome or acute myocardial infarction ≤ 6 months prior to administration of [177Lu]Lu-FAP-2286.
5. Inability to complete the needed investigational and standard imaging examinations due to any reason (e.g., severe claustrophobia, inability to lie still for the entire imaging time).
6. Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the investigator, could prevent adhering to radiation safety instructions.
7. Severe chronic or active HIV infection: a. Participants on effective antiretroviral therapy with undetectable viral load within 6 months prior to the first dose of [177Lu]Lu-FAP-2286 are eligible.
8. Presence of any other condition that may increase the risk associated with study participation or interfere with the interpretation of study results, and, in the opinion of the investigator, would make the participant inappropriate for entry into the study.
9. Non–study-related minor surgical procedure ≤ 5 days, or major surgical procedure ≤ 21 days, prior to the administration of [177Lu]Lu-FAP-2286; in all cases, the participant must be sufficiently recovered and stable before treatment administration.
10. Significant weight loss (> 10% of body weight) within 28 days prior to providing informed consent for this study.
11. The following are exclusion criteria, as applicable: a. Female participants of childbearing potential: i. Refusal to use a highly effective method of contraception or to practice true abstinence during treatment and for 6 months following the last dose of investigational product; ii. Pregnant, suspected pregnancy, or breast feeding; iii. Planning on getting pregnant during treatment and for 6 months following the last dose of investigational product. b. Male participants with female partners of childbearing potential: i. Refusal to use a highly effective method of contraception or to practice true abstinence during treatment and for 6 months following the last dose of investigational product. c. All male participants: i. Refusal to use condoms during sex. ii. Planning to make semen donations during treatment and for 6 months following the last dose of investigational product.
12. Symptomatic and/or untreated CNS metastases or leptomeningeal disease or with primary tumor of CNS origin. a. Participants with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and have completed RT> 2 weeks prior to treatment. Participants may be on corticosteroids if on a stable dose equivalent to prednisone 10 mg daily or less.
13. Received anticancer treatment with chemotherapy, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs ≤ 14 days prior (≤ 28 days prior in case of checkpoint inhibitor therapy and other antibody therapies) to the administration of [177Lu]Lu-FAP-2286.
14. Participants with known hypersensitivity to the active agent or excipients.
15. Severe chronic or active infections (including active tuberculosis, HBV, or HCV infection) requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks before enrollment. Note: Antiviral therapy is permitted for participants with chronic HBV or HCV infection. Participants receiving antivirals at Screening should have been treated for > 2 weeks before enrollment. Inactive hepatitis B surface antigen (HbsAg) carriers treated and stable hepatitis B participants (HBV DNA < 500 IU/mL or < 2500 copies/mL) can be enrolled. Participants with detectable hepatitis B surface antigen (HbsAg) or detectable HBV DNA should be managed per treatment guidelines. Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Investigator-assessed ORR per RECIST v1.1
2. Dose-limiting toxicities (DLTs), adverse events (AEs), serious AEs (SAEs) and clinical laboratory abnormalities

Secondary endpoints 5

1. DOR per RECIST v1.1, as assessed by investigator
2. Confirmed partial response (PR) or complete response (CR), or stable disease (SD) of at least 12 weeks
3. Disease progression according to RECIST v1.1, as assessed by investigator, or death due to any cause
4. AEs, SAEs, and clinical laboratory abnormalities at the RP2D of [177Lu]Lu-FAP-2286 for monotherapy, the RP2D in combination with mFOLFIRINOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC (Phase 2 dose expansion)
5. AEs and SAEs during and after [68Ga]Ga-FAP-2286 administration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 17

Locations

4 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 66 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications