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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04939610




Registration number
NCT04939610
Ethics application status
Date submitted
9/06/2021
Date registered
25/06/2021

Titles & IDs
Public title
A Study of 177Lu-FAP-2286 in Advanced Solid Tumors
Scientific title
LuMIERE: A Phase 1/2, Multicenter, Open-label, Non-randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of 177Lu-FAP-2286 in Patients With an Advanced Solid Tumor
Secondary ID [1] 0 0
CAAA614A12101
Secondary ID [2] 0 0
CO-2286-114
Universal Trial Number (UTN)
Trial acronym
LuMIERE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 68Ga-FAP-2286
Treatment: Drugs - 177Lu-FAP-2286

Experimental: Phase 1: Dose Escalation - Up to 30 patients with solid tumors.

Experimental: Phase 2: Specific Solid Tumors - Up to 192 participants treated with \[177Lu\]Lu-FAP-2286 in tumor-specific participant groups in monotherapy and in combination with chemotherapy.


Treatment: Drugs: 68Ga-FAP-2286
68Ga-FAP-2286 IV administered as imaging agent for PET scan.

Treatment: Drugs: 177Lu-FAP-2286
Phase 1:

Patients with positive uptake of 68Ga-FAP- 2286 will receive a fixed dose of 177Lu-FAP-2286 IV administered every 6 weeks for a maximum of 6 doses. Doses range between 3.7 and 9.25 GBq (100-250 mCi).

Phase 2:

Monotherapy: Patients with positive uptake of 68Ga FAP 2286 will receive a fixed dose of 177Lu FAP 2286 IV administered at the RP2D determined in Phase 1 dose escalation in every 4 weeks.

Combination therapy: Patients with positive uptake of 68Ga FAP 2286 will receive 177Lu-FAP-2286 based on dose escalation (starting with dose level 1) followed by dose expansion at selected dose.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Dose-limiting toxicity (DLTs)
Timepoint [1] 0 0
From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)
Primary outcome [2] 0 0
Phase 1: recommended Phase 2 dose (RP2D)
Timepoint [2] 0 0
From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)
Primary outcome [3] 0 0
Phase 1: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of [177Lu]Lu FAP 2286
Timepoint [3] 0 0
From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)
Primary outcome [4] 0 0
Phase 2: Objective Response Rate (ORR)
Timepoint [4] 0 0
From date of first [177Lu]Lu FAP 2286 treatment until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 59 months
Primary outcome [5] 0 0
Phase 2: Dose-limiting toxicity (DLTs)
Timepoint [5] 0 0
Assessed within 4 weeks of first Lu-FAP2286 treatment
Primary outcome [6] 0 0
Phase 2: recommended Phase 2 dose (RP2D)
Timepoint [6] 0 0
From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)
Primary outcome [7] 0 0
Phase 2: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of [177Lu]Lu FAP 2286
Timepoint [7] 0 0
From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)
Secondary outcome [1] 0 0
Phase 1: Absorbed dose (Gy) estimated in organs and tumor lesions
Timepoint [1] 0 0
From first dose of study drug until disease progression or end of treatment (up to approximately 9 months)
Secondary outcome [2] 0 0
Phase 1: Maximum standardized uptake value (SUVmax) in tumor lesions
Timepoint [2] 0 0
Taken within 2 hours after 68Ga-FAP-2286 IV administration
Secondary outcome [3] 0 0
Phase 1: Comparison of SUVmax in tumor lesions
Timepoint [3] 0 0
From time of screening FDG PET/CT to 68Ga-FAP-2286 PET/CT (up to approximately 1 month)
Secondary outcome [4] 0 0
Phase 1: Concentration of [177Lu]Lu FAP 2286 at the end of infusion (Ceoi)
Timepoint [4] 0 0
From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)
Secondary outcome [5] 0 0
Phase 1: Cmax of [177Lu]Lu FAP 2286
Timepoint [5] 0 0
From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)
Secondary outcome [6] 0 0
Phase 1: Tmax of [177Lu]Lu FAP 2286
Timepoint [6] 0 0
From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)
Secondary outcome [7] 0 0
Phase 1: Area under the curve (AUC) of [177Lu]Lu FAP 2286
Timepoint [7] 0 0
From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)
Secondary outcome [8] 0 0
Phase 1: Clearance (CL) of [177Lu]Lu FAP 2286
Timepoint [8] 0 0
From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)
Secondary outcome [9] 0 0
Phase 1: Volume of distribution (Vd) of [177Lu]Lu FAP 2286
Timepoint [9] 0 0
From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)
Secondary outcome [10] 0 0
Phase 1: Half-life (T1/2) of [177Lu]Lu FAP 2286
Timepoint [10] 0 0
From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)
Secondary outcome [11] 0 0
Phase 1: Objective Response Rate (ORR)
Timepoint [11] 0 0
From date of first [177Lu]Lu FAP 2286 treatment until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 57 months
Secondary outcome [12] 0 0
Phase 1: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of [68Ga]Ga FAP 2286
Timepoint [12] 0 0
Up to approximately 57 months
Secondary outcome [13] 0 0
Phase 2 (Dose expansion): Duration of Response (DoR)
Timepoint [13] 0 0
From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to approximately 83 months
Secondary outcome [14] 0 0
Phase 2 (Dose expansion): Disease Control Rate (DCR)
Timepoint [14] 0 0
From date of first [177Lu]Lu FAP 2286 treatment until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 83 months
Secondary outcome [15] 0 0
Phase 2 (Dose expansion): Progression-free survival (PFS)
Timepoint [15] 0 0
From date of first [177Lu]Lu FAP 2286 treatment until date of progression or date of death from any cause, whichever come first, assessed up to 83 months
Secondary outcome [16] 0 0
Phase 2 (Dose expansion): Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of [177Lu]Lu FAP 2286 at the RP2D
Timepoint [16] 0 0
Up to approximately 83 months
Secondary outcome [17] 0 0
Phase 2: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of [68Ga]Ga FAP 2286
Timepoint [17] 0 0
Up to approximately 83 months

Eligibility
Key inclusion criteria
Eligible participants must meet the following inclusion criteria. The criteria below apply to participants enrolling in Phase 1 and Phase 2, unless otherwise specified.

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:

1. 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.

For Phase 1 only:
8. Have a histologically and/or cytologically confirmed advanced/metastatic solid tumor not amenable to treatment with curative intent:

a. Tumor must be refractory to or have progressed following prior treatment and have no satisfactory alternative treatment options.

For Phase 2 only:
9. 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.

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.

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 inhibitor (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.

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 inhibitor (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.

l. Breast cancer monotherapy group i. HR positive 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.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who meet any of the following criteria will be excluded from the study. The criteria below apply to participants enrolling in Phase 1 or Phase 2.

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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:

1. History of second malignancy that has been successfully treated, with no evidence of active cancer for 3 years prior to enrollment;
2. Surgically cured low-risk tumors, such as early-stage cervical or endometrial cancer, any cancer in situ, or non-melanoma skin cancers; and
3. 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. 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.
3. 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.
4. 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.
5. Ongoing adverse effects from anticancer treatment NCI-CTCAE v5.0 (or higher) Grade 1, with the exception for alopecia and vitiligo.

Exclusion criteria 6 and 7 are removed with Protocol Amendment 7. 8. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

1. 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;
2. Corrected QT interval (Fridericia's formula) > 450 msec for males or > 470 msec for females at Screening; or
3. Acute coronary syndrome or acute myocardial infarction = 6 months prior to administration of [177Lu]Lu FAP 2286.

9. 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.

10. 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.

Exclusion criteria 11 and 12 are removed with Protocol Amendment 7. 13. 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.

14. 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.

15. Significant weight loss (> 10% of body weight) within 28 days prior to providing informed consent for this study.

16. 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.

17. 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).

18. Participants with known hypersensitivity to the active agent or excipients. 19. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2028
Actual
Sample size
Target
222
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred Hopsital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-689-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04939610