177LU-FAP-2286 for Non-small cell lung cancer | Pancreatic ductal adenocarcinoma | Metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF) prior to any study-specific evaluation."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Be ≥ 18 years of age at the time the ICF is signed."}
• {"criterion_text":"- Have consented to submission of fresh or archival tumor tissue, if available."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have an Eastern Oncology Group (ECOG) performance status of 0 or 1."}
• {"criterion_text":"- Have a life expectancy of ≥ 6 months."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Significant weight loss (> 10% of body weight) within 28 days prior to providing informed consent for this study."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants with known hypersensitivity to the active agent or excipients."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Ongoing adverse effects from anticancer treatment NCI-CTCAE v5.0 (or higher) Grade 1, with the exception for alopecia and vitiligo."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Investigator-assessed ORR per RECIST v1.1","definition_or_measurement_approach":"Objective response rate (ORR) assessed by investigator using RECIST v1.1 criteria."}
• {"endpoint_text":"- Dose-limiting toxicities (DLTs), adverse events (AEs), serious AEs (SAEs) and clinical laboratory abnormalities","definition_or_measurement_approach":"Safety endpoints assessed by reporting of DLTs, AEs, SAEs and clinical laboratory abnormalities (per study safety reporting procedures; NCI-CTCAE referenced elsewhere in protocol)."}

Secondary endpoints

• {"endpoint_text":"- DOR per RECIST v1.1, as assessed by investigator","definition_or_measurement_approach":"Duration of response assessed by investigator according to RECIST v1.1."}
• {"endpoint_text":"- Confirmed partial response (PR) or complete response (CR), or stable disease (SD) of at least 12 weeks","definition_or_measurement_approach":"Tumor response categories (PR/CR/SD) confirmed per RECIST v1.1; SD defined as stable disease for ≥12 weeks."}
• {"endpoint_text":"- Disease progression according to RECIST v1.1, as assessed by investigator, or death due to any cause","definition_or_measurement_approach":"Progression-free survival/progression events assessed per RECIST v1.1 by investigator; death recorded as event."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Safety assessed by frequency and severity of AEs/SAEs and lab abnormalities at recommended Phase 2 doses for monotherapy and combinations (per study safety reporting)."}
• {"endpoint_text":"- AEs and SAEs during and after [68Ga]Ga-FAP-2286 administration","definition_or_measurement_approach":"Adverse events and serious adverse events recorded during and after administration of the diagnostic/selection agent [68Ga]Ga-FAP-2286."}

Methods

• Site-based recruitment through participating hospitals/oncology and nuclear medicine departments (hospital site contact and department lists provided).
• Use of recruitment materials and patient-facing information (posters, trifold brochures, 'Understanding Your Study' guides and study discussion guides) for outreach.
• Referral letters and GP/primary care information letters to clinicians to identify potential participants.

Belgium

Earliest CTIS Part Ii Submission Date

23-07-2025

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

36

Number Of Sites

4

Number Of Participants

7

Spain

Earliest CTIS Part Ii Submission Date

21-05-2025

Latest Decision Or Authorization Date

26-08-2025

Processing Time Days

97

Number Of Sites

7

Number Of Participants

10

France

Earliest CTIS Part Ii Submission Date

21-05-2025

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

98

Number Of Sites

5

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

21-05-2025

Latest Decision Or Authorization Date

26-08-2025

Processing Time Days

97

Number Of Sites

8

Number Of Participants

9

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

code 12

Name

Syneos Health Inc.

Responsibilities

code 6

Name

Psi Cro AG

Responsibilities

code 1; accountable for subject records and CRFs, progress of enrolment, IMPs storage and dispensing

Name

Icon Laboratory Services Inc.

Responsibilities

Provide sample collection kits

Name

WCG Clinical Inc.

Responsibilities

Central IRB Submissions

Third parties

• {"country":"United Kingdom","full_name":"Charles River Laboratories Edinburgh Limited","duties_or_roles":"Compound Radio-metabolite analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"code 12","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories International Inc.","duties_or_roles":"Compound Radio-metabolite analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Provide sample collection kits, sample storage and shipping to analysis labs","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"1) Randomization of Patients. 2) Management of drug supply logistics and dispensing; code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Provide sample collection kits, sample storage and shipping to analysis labs","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Provide sample collection kits","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG reading","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Central IRB Submissions","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Sample storage and shipping to analysis labs","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Study materials and recruitment materials","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Invicro LLC","duties_or_roles":"Central Imaging and dosimetry (MRI/CT)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"Immunohistochemistry analysis (Newly obtained/Archival tumor) - Biomarkers (Tumor Tissue) IHC","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Singapore","full_name":"Labcorp Development (Asia) Pte Ltd","duties_or_roles":"Provide sample collection kits, sample storage and shipping to analysis labs","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Psi Cro AG","duties_or_roles":"code 1; accountable for subject records and CRFs, progress of enrolment, IMPs storage and dispensing","organisation_type":"Pharmaceutical company"}