ADDENDUM 3 AL CONTRATTO PER LA CONDUZIONE DELLA SPERIMENTAZIONE CLINICA SU MEDICINALI“Studio multicentrico di fase III, randomizzato, in aperto, volto a valutare l’efficacia e la sicurezza Giredestrant adiuvante rispetto alla monoterapia endocrina...

ADDENDUM 3 AL CONTRATTO PER LA CONDUZIONE DELLA SPERIMENTAZIONE CLINICA SU MEDICINALI “Studio multicentrico di fase III, randomizzato, in aperto, volto a valutare l’efficacia e la sicurezza Giredestrant adiuvante rispetto alla monoterapia endocrina adiuvante di scelta del medico in pazienti con carcinoma mammario precoce positivo al recettore degli estrogeni e HER2 negativo” – lidERA”	ADDENDUM 3 TO CLINICAL INVESTIGATION AGREEMENT FOR THE DRUGS “A Phase III,Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and safety of adjuvant Giredestrant compared with Physician's Choice of Adjuvant Endocrine Monotherapy in patients with Estrogen Receptor-Positive, HER2 Negative Early Breast Cancer” – lidERA”
SOTTOSCRITTO TRA	SIGNED BY
Azienda USL Toscana Centro (d'ora innanzi denominato/a “Ente"), con sede legale in Xxxxxxx, X.xxx Xxxxx Xxxxx Xxxxx, 0 – 00000 Xxxxxxx, C.F. e P. IVA n. 06593810481, in persona del Legale Rappresentante, Dr. Xxxxx Xxxxxxxx Xxxxxxx, in qualità di Direttore Generale, che ha munito di idonei poteri di firma del presente atto il Direttore Area Valutazione performance e welfare Xxxx. Xxxxxxxxxx Xxxxx, CF: SRGLSN61H12F205M, (d'ora innanzi denominato “Delegato”)	Azienda USL Toscana Centro (hereinafter the “Entity"), headquartered in Xxxxxxx, X.xxx Xxxxx Xxxxx Xxxxx, 0 – 00000 Xxxxxxx, tax code and VAT no. 06593810481, through its Legal Representative Dr. Xxxxx Xxxxxxxx Xxxxxxx, in the capacity of Director General, who has granted the Director Performance and Welfare Evaluation the Health Department Dr Xxxxxxxxxx Xxxxx, Fiscal Code: XXXXXX00X00X000X, (hereinafter „Delegate”), with the powers to enter into this Agreement
E	AND
Translational Research In Oncology (TRIO), con sede legale in in Xxxxx 0000, 0000-000xx Xxxxxx XX, Xxxxxxxx, Xxxxxxx, Xxxxxx X0X 0X0, P.IVA n. 891637928RT0001, in persona del Legale Rappresentante, Dott.ssa Xxxxxxx Xxx, in qualità di Direttore del Dipartimento di Gestione del Dipartimento del Progetto (PM), (d'ora innanzi denominata "CRO"), che agisce in nome e per conto di X.Xxxxxxxx-LA ROCHE LTD (d'ora innanzi denominata "Promotore"), in forza di idonea delega conferita in data 21 Maggio 2021	Translational Research In Oncology (TRIO, headquartered in Canada, at Xxxxx 0000, 0000- 000xx Xxxxxx XX, Xxxxxxxx, Xxxxxxx, X0X 0X0, VAT no. 891637928RT0001, through its Legal Representative, Dr Xxxxxxx Xxx as Director Director Project Management Department (PM) , (hereinafter the "CRO"), acting in the name and on behalf of X.Xxxxxxxx-LA ROCHE LTD (hereinafter the "Sponsor"), by virtue of the authority granted on 21 May 2021

Premesso che:	Whereas:
• In data 05/07/2022 è stato stipulato tra l’Ente e la CRO un contratto (di seguito nominato il “Contratto”) per lo svolgimento dello Studio Clinico “Studio multicentrico di fase III, randomizzato, in aperto, volto a valutare l’efficacia e la sicurezza Giredestrant adiuvante rispetto alla monoterapia endocrina adiuvante di scelta del medico in pazienti con carcinoma mammario precoce positivo al recettore degli estrogeni e HER2 negativo” (di seguito "Sperimentazione"), codice EudraCT n. 0000-000000-00, presso la SOC Oncologia Medica del Nuovo Ospedale di Empoli San Xxxxxxxx di seguito (“Centro di sperimentazione”), sotto la responsabilità della Dott.ssa Xxxxxxxxx Xxxxxxxx, in qualità di Responsabile scientifico della Sperimentazione (di seguito “Sperimentatore principale”);	• On 05/07/2022, the Entity and the CRO entered into an agreement (hereinafter referred to as the “Agreement”) to conduct the Clinical Trial “A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and safety of adjuvant Giredestrant compared with Physician's Choice of Adjuvant Endocrine Monotherapy in patients with Estrogen Receptor-Positive, HER2 Negative Early Breast Cancer” (hereinafter referred to as the “Trial”), EudraCT code no. 0000-000000-00, at the SOC Medical Oncology in Nuovo Ospedale di Empoli San Xxxxxxxx (the “Trial Centre”) under the responsibility of Dr. Xxxxxxxxx Xxxxxxxx, as the Scientific Director of the Trial (the “Principal Investigator”);
• In data 11/05/2023 è stato stipulato tra le parti l’addendum 1 al contratto, in seguito all’approvazione del Protocollo versione3 del 30/06/2022.	• On 11/05/2023, addendum 1 to the Agreement was entered into between the parties, following the approval of the Protocol Version 3 dated 06/30/2022.
• Si è reso necessario emendare il Protocollo versione 2 del 30/06/2021, presentando, con l’emendamento 2 al Protocollo, la versione 3 del 30/06/2022;	• It became necessary to amend the Protocol version 2 of 30/06/2021, submitting, with Amendment 2 to the Protocol, version 3 of 06/30/2022;
• Si è reso necessario emendare il Protocollo versione 3 del 30/06/2022, presentando, con l’emendamento 3 alProtocollo, la versione 4 del 21/12/2022;	• It became necessary to amend the Protocol version 2 of 30/06/2022, submitting, with Amendment 3 to the Protocol, version 4 of 21/12/2022;
•Si è reso necessario emendare il Protocollo versione 4 del 21/12/2022, presentando,	•It became necessary to amend the Protocol version 4 of 21/12/2022, submitting, with

con l’emendamento 4 al Protocollo, la versione 5 del 25/08/2023;	Amendment 4 to the Protocol, version 5 of 25/08/2023;
• La versione 4 del Protocollo ha ottenuto l’approvazione di AIFA in data23/05/2023 e del Comitato Etico Coordinatore (CEC), IRCCS Xxxxxxx di Napoli in data 05/04/2023.	• Version 4 of the Protocol was approved by Italian Medicines Agency (AIFA) on 23/05/2023 and by the Coordinating Ethics Committee (CEC), IRCCS Xxxxxxx di Napoli on 05/04/2023.
• Il Protocollo v.4 prevede modifiche allo schema delle attività, comportando un’ulteriore modifica al compenso riconosciuto all’Ente e stabilito nel relativo contratto e addendum 1.	• Protocol v.4 foresees changes to the scheme of activities and visits, entailing an additional modification to the reimbursement assigned to the Entity and set out in the relevant agreement and addendum 1.
• Il Protocollo v.4, in particolare, prevede - l’incremento delle visite in cui eseguire la misurazione della Coagulazione (PT, PTT e INR) a visite alterne a partire dal Ciclo 18 Giorno 1 - l’aggiunta del test di gravidanzaanche per la visita ET Follow up:	• Protocol v.4, in particular, provides for: - the increase of visits at which to perform coagulation measurement ((PT, PTT and INR) on alternate visits from C18 D1. - the addition of the pregnancy test also for the Next ET Follow up visit
• La versione 5 del Protocollo ha ottenuto l’approvazione di AIFA in data18/01/2024 e del Comitato Etico Territoriale (CET), Campania 1 in data 29/11/2023.	• Version 5 of the Protocol was approved by Italian Medicines Agency (AIFA) on 18/01/2024 by the Territorial Ethics Committee (CET), Campania1 on 29/11/2023.
• Il Protocollo v.5 prevede modifiche allo schema delle attività, comportando un’ulteriore modifica al compenso riconosciuto all’Ente e stabilito nel relativo contratto e addendum 2.	• Protocol v.5 foresees changes to the scheme of activities and visits, entailing an additional modification to the reimbursement assigned to the Entity and set out in the relevant agreement and addendum 2.
Tutto ciò premesso, tra le Parti si conviene e si stipula quanto segue:	Now therefore, in consideration of the foregoing, it is hereby agreed as follows:
1. l’Ente e la CRO convengono di stipulare un atto integrativo al Contratto:	1. Entity and CRO agree to enter into an Addendum to the Agreement:

1.1. Le premesse sono parte integrante e sostanziale del presente documento (di seguito nominato l'"Addendum 3").	1.1. The preamble is an integral and substantive part of this document (hereinafter referred to as the "Addendum 3").
1.2. La terminologia utilizzata nel Contratto è valida anche per il presente Addendum.	1.2. The terminology used in the Agreement shall also apply to this Addendum.
2. L’Ente e la CRO concordano di modificare alcuni articoli del Contratto come segue:	2. The Entity and the CRO agree to amend certain articles of the Agreement as follows:
2.1. L’art. 6.1 del Contratto (“Corrispettivo”), è modificato come segue: Il corrispettivo pattuito per paziente eleggibile, valutabile e completato secondo il Protocollo e per il quale è stata compilata validamente la relativa eCRF, comprensivo di tutte le spese sostenute dall’Ente per l’esecuzione della presente Sperimentazione e dei costi a compensazione di tutte le attività ad essa collegate, è pari ad €10710.00 (e complessivi € 21913.00 ) a paziente incluso nel braccio di trattamento; €10260.00 (e complessivi € 21463.00 ) a paziente incluso nel braccio di controllo) per n. 20 pazienti, come meglio dettagliato nel Budget qui allegato (Allegato “A” parte 1).	2.1. Section 6.1 of the Agreement ("Fee") is amended as follows: The agreed fee per eligible, assessable and completed patient according to the Protocol and for whom the relevant eCRF has been validly completed, inclusive of all expenses incurred by the Entity for the implementation of this trial and the costs to compensate for all related activities related to it, is €10710.00 (and a total of € 21913.00 ) per patient included in the treatment arm; €10260.00 (and a total of €21463.00 ) per patient included in the control arm) for n. 20 patients, as better detailed in the attached Budget (Annex "A" part 1).
2.2. La sezione A2 Oneri e compensi - parte 1 e parte 2 dell’allegato A–BUDGET ALLEGATO ALLA CONVENZIONE ECONOMICA del Contratto viene sostituito con l’Allegato A2 Oneri e compensi parte 1 e parte 2 dell’Addendum.	2.2. Section A2 Costs and payments - Part 1 and Part 2 of Appendix A – BUDGET ANNEX TO FINANCIAL AGREEMENT to the Agreement is hereby replaced with Appendix A2 to Costs and payments part 1 and part 2 of the Addendum.
3. Tutte gli altri termini e le altre condizioni previsti e contenuti nel Contratto restano pienamente valide, efficaci ed invariate.	3. All other terms and conditions provided for and contained in the Agreement shall remain in full force, effect and unchanged.

T

TRIO045_ITA_MARTELLA_ Addendum 3 Prot.V.5 Pag.5a13

4. Oneri fiscali 4.1. Il presente addendum viene sottoscritto con firma digitale ai sensi dell’art. 24 del D. Lgs. 82/2005, giusta la previsione di cui all’art. 15, comma 2bis della Legge n. 241/1990, come aggiunto dall’art. 6, D.L. 18/10/2012, n. 179, convertito in Legge 17/12/2012 n. 22. Le imposte e tasse inerenti e conseguenti alla stipula del presente Addendum, ivi comprese l’imposta di bollo sull’originale informatico di cui all’art. 2 della Tabella Allegato A – tariffa parte I del DPR n. 642/1972 e l’imposta di registro devono essere versate, nel rispetto della normativa applicabile. 4.2. L’imposta di bolloè assolta dal promotore con le marche da bollo da 16 € contrassegnate dai codici: ID: 01230216943535 ID: 01230216943524 ID: 01230216982669 ID: 01230216982658	4. Fiscal obligations 4.1 This Addendum is signed digitally in accordance with Article 24 of legislative decree 82/2005, in accordance with the provisions of Article 15 paragraph 2A of Law 241/1990 as supplemented by article 6, decree law 18/10/2012, no. 179, converted into Law no. 22 of 17/12/2012. All the taxes and duties relating to or resulting from the stipulation of this Addendum, including the revenue stamp on the digital original as referred to in Article 2 of the table in Annex A – tariff part I of Presidential Decree 642/1972, and the registration tax, must be paid in accordance with the applicable regulations. 4.2 Stamp duty is paid by the Sponsor with the 16 € marked with the following codes:
Le Parti si danno reciprocamente atto che il presente Xxxxxxxx è stato accettato in ogni sua parte e che non trovano pertanto applicazione le disposizioni di cui agli artt. 1341 Codice Civile.	The Parties confirm that every part of this Addendum has been accepted and therefore the provisions of Article 1341 of the Italian Civil Code will not apply.
Letto, approvato e sottoscritto	Read, approved and undersigned
Paris , li 29 M/ ay/ 2024 | 13:13 MDT Per la CRO Rappresentante legale, in qualità di Direttore PM Dott.ssa Xxxxxxx Xxx Firma	Paris , 29 /May/ 2024 | 13:13 MD For the CRO Legal Representative, as Director PM Dr. Xxxxxxx Xxx Signature

, li   / /   Per I’Ente Il Delegato XXXXXXXXXX XXXXX Regione Toscana/01386030488 Direttore Area Valutazione per12f.o06r.2m024a13n:53c:5e3 e GMT+00:00 welfare Xxxx. Xxxxxxxxxx Xxxxx Firma

,   / /    For the Entity XXXXXXXXXX XXXXX The Delegate Regione Toscana/01386030488 Director Performance and welfare12.e06v.20a24lu13a:53t:5i3on GMT+00:00 area Dr. Xxxxxxxxxx Xxxxx Signature

A2. Oneri e compensi Parte 1 - Oneri fissi e Compenso per paziente incluso nello studio ‐ Fornitura del/i Medicinale/i Sperimentale/i e/o di ogni altro materiale in sperimentazione o necessario allo svolgimento della stessa affinché non vi sia aggravio di costi a carico del S.S.N. (kit diagnostici, dispositivi medici, ecc.). ‐ Compenso lordo a paziente incluso nello studio: €10710.00 per i pazienti che sono inclusi nel braccio di trattamento; €10260.00 per i pazienti che sono inclusi nel braccio di controllo. ‐ Compenso per il Centro sperimentale a paziente completato (Compenso a paziente arruolato tutti i costi sostenuti dall’Ente per la sperimentazione1): € 21913.00 per i pazienti che sono inclusi nel braccio di trattamento e €21463.00 per i pazienti che sono inclusi nel braccio di controllo. ‐ Fasi economiche intermedie (nel caso in cui i pazienti non completino l’iter sperimentale): Visita Compenso/paziente:

A2. Costs and payments Part 1 – Fixed costs and payment per patient included in the study Include, by way of example, the following items: ‐ Supply of the Trial Drug(s) and/or of any other materials required for the trial provided that there are no extra costs for the National Health Service (diagnostics kits, medical devices, etc.). ‐ Gross payment per patient included in the study: € 10710.00 for the patients in the treatment arm and €10260.00 for patients in the control arm. ‐ Payment per trial Centre for each completed patient (Payment for enrolled patient – company overheads – all the costs incurred by the Entity for the trial2): €21913.00 for the patients in the treatment arm and €21463.00 for patients in the control arm. ‐ Interim financial phases (if the patients do not complete the trial procedure): Examination: payment per patient:

1 • costi amministrativi generali, costi sostenuti dal servizio farmaceutico per la gestione del/dei farmaco/i oggetto della Sperimentazione

2 • general admin costs, costs incurred by the Pharmacy service in managing the Trial drug(s).

		BRACCIO A	BRACCIO B (controllo) Costo unitario (IVA esclusa) €/ARM B (control) Unit cost (VAT excluded) €
		(Giredestrant) Costo
	Visite/Visits	unitario (IVA esclusa) €/ARM A (Giredestrant)
		Unit cost (VAT
		excluded) €
	Selezione/Screening	440	440
	Ciclo 1 Giorno 1/Cycle
	1 Day 1	430	360
	Ciclo 2 Giorno 1/Cycle
	2 Day 1	360	310
	Ciclo 3 Giorno 1/Cycle
	3 Day 1	380	350
	Ciclo 6 Giono 1/Cycle
	6 Day 1	410	380
	Ciclo 9 Giorno 1/Cycle
	9 Day 1	370	350
	Ciclo 12 Giorno
	1/Cycle 12 Day 1	450	430
	Ciclo 15 Giorno
	1/Cycle 15 Day 1	350	350
	Ciclo 18 Giorno
	1/Cycle 18 Day 1	430	420
	Ciclo 21 Giorno
	1/Cycle 21 Day 1	350	350
	Ciclo 24 Giorno
	1/Cycle 24 Day 1	500	480
	Ciclo 27 Giorno
	1/Cycle 27 Day 1	300	300
	Ciclo 30Giorno 1/Cycle
	30 Day 1	430	420
	Ciclo 33 Giorno
	1/Cycle 33 Day 1	300	300
	Ciclo 36 Giorno
	1/Cycle 36 Day 1	500	480
	Ciclo 39 Giorno
	1/Cycle 39 Day 1	300	300

	Ciclo 42 Giorno
	1/Cycle 42 Day 1	430	420
	Ciclo 45 Giorno
	1/Cycle 45 Day 1	300	300
	Ciclo 48 Giorno
	1/Cycle 48 Day 1	500	480
	Ciclo 51 Giorno
	1/Cycle 51 Day 1	300	300
	Ciclo 54 Giorno
	1/Cycle 54 Day 1	430	410
	Ciclo 57 Giorno
	1/Cycle 57 Day 1	300	300
	Ciclo 60 Giorno
	1/Cycle 60 Day 1	500	480
	Ciclo 63 Giorno
	1/Cycle 63 Day 1	365	350
	Visita di fine
	trattamento-
	interruzione
	anticipate/End of
	Tx/Early D/C	515	480
	Visita di follow up in
	caso di soluzione
	anticipata/Early
	Termination Follow-up
	visit (Q3M)	290	290
	FU a lungo termine per
	recidica (Q3M)/Long
	Term Follow-Up for
	recurrence (Q3M)	100	85
	Long-Term Follow-Up
	W/PROs	155	135
	Follow up a lungo
	termine (6M) (attese
	10 visite)/Long-term
	Follow-Up (Q6M) (10
	visits expected)	100	85
	Soppravvivenza Lungo
	Termine (Q6M)/Long-
	Term Survival FU
	(Q6M)	125	125
	TOTALE/TOTAL	10710	10260

Nel costo visita sono compresi tutti gli esami/procedure e la raccolta dei campioni previsti dal protocollo per ogni singola visita. Per ogni visita non programmata (Unscheduled visit) verrà corrisposto all’Ente l’importo di €260,00.	The cost of the visit includes all the examinations/procedures and the collection of samples foreseen by the protocol for each individual visit. An amount of €260,00 will be paid to the organisation for each unscheduled visit.
Per i pazienti che risulteranno screening failure sarà retribuito l’intero corrispettivo della visita di screening indicato nella tabella sopra riportata, oltre alle procedure, indicate nel contratto ed eseguite dopo la firma del consenso che verranno comunicate dall’Ente, purché i pazienti siano stati selezionati correttamente e la mancata idoneità all’arruolamento sia imputabile a cause non prevedibili dallo Sperimentatore. Pertanto, non sarà rimborsato il corrispettivo per motivi che avrebbero potuto essere identificati nel corso di un’accurata anamnesi.	For patients who are found to be screening failures, the entire fee for the screening visit indicated in the table above will be paid, in addition to the procedures indicated in the agreement and carried out after the signing of the consent, which will be communicated by the organisation, provided that the patients have been correctly selected and the lack of eligibility for enrolment is attributable to causes not foreseeable by the investigator. Therefore, no reimbursement will be made for reasons that could have been identified in the course of a thorough medical history.
Il Promotore fornirà all’Ente il materiale per eseguire il test di gravidanza su urine. Nel caso in cui il menzionato test dovesse risultare positivo, verrà eseguito l’esame su sangue e verrà rimborsato secondo il tariffario riportato nella parte 2 del presente allegato	The Sponsor will provide the Entity with the material to perform the urine pregnancy test. In the event that the aforementioned test will be positive, the serum test will be performed and will be reimbursed according to the rate shown in part 2 of this annex
Parte 2 Costi aggiuntivi per esami strumentali e/o di laboratorio da effettuarsi sulla base del Tariffario	Part 2 Additional costs for instrumental tests and/or lab tests to be carried out according to the Tariff
Dettaglio dei costi aggiuntivi (gli importi indicati relativi alle prestazioni potranno subire aggiornamenti e revisioni a seguito di atti/disposizioni adottati dalla Regione Toscana e che trovano applicazione dalla data di decorrenza dagli stessi atti):	Breakdown of additional costs (the amounts payable for the services may be updated or revised following decisions/measures taken by the region of Toscana and will apply from the effective date of those decisions/measures):

	Voci fatturabili/Invoiceable Items	Costo unitario € (IVA esclusa) /Unit Cost € (excluded VAT)	Condizioni supplementari /Additional Terms
	Visita infermieristica tramite telefono/Mobile Nursing Visit	190,00	Pagato secondo eCRF se la visita del giorno 1 viene eseguita come visita infermieristica mobile (cicli 27, 33, 39, 45, 51, 57 e follow-up a lungo termine)/ Paid by eCRF if Day 1 visit is performed by mobile nurse (Cycles 27, 33, 39, 45, 51, 57, and Long-Term Follow-Up)
	Early- Termination Follow-up visit (Q3M)	290.00	Paid by eCRF (one unit is already included in patient fee)
	Long-Term Follow-Up (Q6M)	100.00	Paid by eCRF (one unit is already included in patient fee)
	Long-Term Follow-Up w/PROs (Q6M)	155.00	Paid by eCRF (one unit is already included in patient fee)
	Single 12-Lead ECG	49,00	Screening, Cycles 1, 3, 6,9,12, unscheduled visit
	ECG a 12 derivazioni – triplice/ Triplicate 12-Lead ECG	67,00	Solo per confermare anormalie clinicamente significanti/Only to confirm clinically significant abnormalities.
	Follitropina /FSH	8,00	Per donne in premenopausa/perimenopausa e per uomini e donne che ricevono un agonista LHRH./ For premenopausal/perimenopausal women and men/women receiving an LHRH agonist.
	Estradiolo/Estradiol	14,00	Per donne in premenopausa/perimenopausa e per donne che ricevono un agonista LHRH. For premenopausal/perimenopausal women and women receiving an LHRH agonist.
	Pannello epatiti virali: HBV e HCV /Hepatitis Panel (HBV and HCV)	38,00	Se noto o sospetto di infezione/ If known or suspected of infection.

	VIRUS EPATITE B DNA/HBV DNA	91,00	Se noto o sospetto di infezione/ If known or suspected of infection.
	HCV RNA	111,00	Se noto o sospetto di infezione/ If known or suspected of infection.
	Mammografia Bilaterale/ Mammogram (bilateral)	45,00
	Risonanza Magnetica Nucleare (Rm) Della Mammella /Breast MRI (bilateral) without Contrast	170,00
	Risonanza Magnetica Nucleare (Rm) Xxxxx Xxxxxxxx /Breast MRI (bilateral) with Contrast	250
	TC combinata del torace, dell'addome e della pelvi con contrasto /Combined Chest, Abdomen, Pelvic CT Scan with Contrast	510,00
	TC combinata del torace, dell'addome e della pelvi senza contrasto /Combined Chest, Abdomen, Pelvic CT Scan without Contrast	322,00
	TC del torace con contrasto/ Chest CT Scan with Contrast	170,00
	TC pelvica con contrasto /Pelvic CT Scan with Contrast	170,00
	TC dell'addome con contrasto/ Abdomen CT Scan with Contrast	170,00
	TC del torace senza contrasto/ Chest CT Scan without Contrast	102,00
	Abdomen CT Scan without Contrast	110,00
	TC dell'addome senza contrasto/ Pelvic CT Scan without Contrast	110,00
	Risonanza magnetica del torace con contrasto /Chest MRI with Contrast	250,00
	Risonanza magnetica dell'addome con contrasto/ Abdomen MRI with Contrast	250,00

	Risonanza magnetica pelvica con contrasto /Pelvic MRI with Contrast	250,00
	Scansione ossea /Bone Scan	162,00
	Risonanza magnetica dell'intero corpo /Whole Body MRI	750,00
	Scansione PET dell'intero corpo/ Whole Body PET Scan	1.082,00
	Indagine scheletrica a raggi X; limitata (per le metastasi)/X-Ray Skeletal Survey; Limited (for metastases)	110,00
	Densità minerale ossea TC (scheletro assiale)/Bone Mineral Density CT (axial skeleton)	110,00
	Somministrazione di agonista LHRH (per ciclo)/LHRH agonist administration (per cycle)	50,00	Solo se non è considerato uno standard di cura. / Only if not considered standard of care.
	Assorbimento a raggi X a doppia energia (DXA), scheletro assiale/ Dual-energy X-ray absorptiometry (DXA), axial skeleton	62,00
	Biopsia del tumore fresco /Fresh Tumor Biopsy	160,00
	Preparazione e spedizione del tessuto tumorale /Tumor Tissue Preparation and shipment	200,00
	Test di gravidanza su siero/ Serum pregnancy test	15,00	Test di gravidanza su siero, allo screening, per tutte le donne in età fertile, da ripetere in caso di positività del test delle urine (I test di gravidanza delle urine sono forniti dallo Sponsor) /All women of childbearing potential will have a serum test at screening to be repeated in case of urine test positivity (urine pregnancy tests provided by the Sponsor)

Costi del sito/Site Costs	Costi € (IVA esclusa)/Cost € (excluded VAT)
Archiviazione (per 25 anni secondo il nuovo regolamento) /Archiving (for 25 years according the new regulation)	800,00
Gestione e conservazione dei farmaci /Drug management and storage	750,00

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Xxxxxxx XXXXXXXX		Sent: 5/29/2024 1:12:10 PM
xxxxxxx.xxxxxxxx-xxx@xxxxxxxxxxx.xxx
Security Level: Email, Account Authentication
(Required)
Electronic Record and Signature Disclosure:
Accepted: 4/26/2023 6:08:11 AM ID: eea6b3c0-5373-4b5e-aa90-7af81301d8e3

Madalina Butiseaca xxxxxxxx.xxxxxxxxx@xxxxxxxxxxx.xxx

Security Level: Email, Account Authentication (Required)

Electronic Record and Signature Disclosure:

Sent: 5/29/2024 1:12:11 PM

Carbon Copy Events	Status	Timestamp
Not Offered via DocuSign
Witness Events	Signature	Timestamp
Notary Events	Signature	Timestamp
Envelope Summary Events	Status	Timestamps
Envelope Sent	Hashed/Encrypted	5/29/2024 1:12:11 PM
Certified Delivered	Security Checked	5/29/2024 1:12:41 PM
Signing Complete	Security Checked	5/29/2024 1:13:40 PM
Completed	Security Checked	5/29/2024 1:13:40 PM
Payment Events	Status	Timestamps
Electronic Record and Signature Disclosure

Electronic Record and Signature Disclosure created on: 7/11/2018 11:00:03 AM Parties agreed to: Xxxxxxx XXXXXXXX

CONSUMER DISCLOSURE

From time to time, TRIO (we, us or Company) may be required by law to provide to you certain written notices or disclosures. Described below are the terms and conditions for providing to you such notices and disclosures electronically through the DocuSign, Inc. (DocuSign) electronic signing system. Please read the information below carefully and thoroughly, and if you can access this information electronically to your satisfaction and agree to these terms and conditions, please confirm your agreement by clicking the ‘I agree’ button at the bottom of this document.

Getting paper copies

At any time, you may request from us a paper copy of any record provided or made available electronically to you by us. You will have the ability to download and print documents we send to you through the DocuSign system during and immediately after signing session and, if you elect to create a DocuSign signer account, you may access them for a limited period of time (usually 30 days) after such documents are first sent to you. After such time, if you wish for us to send you paper copies of any such documents from our office to you, you will be charged a

$0.00 per-page fee. You may request delivery of such paper copies from us by following the procedure described below.

Withdrawing your consent

If you decide to receive notices and disclosures from us electronically, you may at any time change your mind and tell us that thereafter you want to receive required notices and disclosures only in paper format. How you must inform us of your decision to receive future notices and disclosure in paper format and withdraw your consent to receive notices and disclosures electronically is described below.

Consequences of changing your mind

If you elect to receive required notices and disclosures only in paper format, it will slow the speed at which we can complete certain steps in transactions with you and delivering services to you because we will need first to send the required notices or disclosures to you in paper format, and then wait until we receive back from you your acknowledgment of your receipt of such paper notices or disclosures. To indicate to us that you are changing your mind, you must withdraw your consent using the DocuSign ‘Withdraw Consent’ form on the signing page of a DocuSign envelope instead of signing it. This will indicate to us that you have withdrawn your consent to receive required notices and disclosures electronically from us and you will no longer be able to use the DocuSign system to receive required notices and consents electronically from us or to sign electronically documents from us.

All notices and disclosures will be sent to you electronically

Unless you tell us otherwise in accordance with the procedures described herein, we will provide electronically to you through the DocuSign system all required notices, disclosures, authorizations, acknowledgements, and other documents that are required to be provided or made available to you during the course of our relationship with you. To reduce the chance of you inadvertently not receiving any notice or disclosure, we prefer to provide all of the required notices and disclosures to you by the same method and to the same address that you have given us. Thus, you can receive all the disclosures and notices electronically or in paper format through the paper mail delivery system. If you do not agree with this process, please let us know as described below. Please also see the paragraph immediately above that describes the consequences of your electing not to receive delivery of the notices and disclosures

electronically from us.

How to contact TRIO:

You may contact us to let us know of your changes as to how we may contact you electronically, to request paper copies of certain information from us, and to withdraw your prior consent to receive notices and disclosures electronically as follows:

To contact us by email send messages to: xxxxx.xxxxxxxxxxx@xxxxxxxxxxx.xxx

To advise TRIO of your new e-mail address

To let us know of a change in your e-mail address where we should send notices and disclosures electronically to you, you must send an email message to us at xxxxx.xxxxxxxxxxx@xxxxxxxxxxx.xxx and in the body of such request you must state: your previous e-mail address, your new e-mail address. We do not require any other information from you to change your email address..

In addition, you must notify DocuSign, Inc. to arrange for your new email address to be reflected in your DocuSign account by following the process for changing e-mail in the DocuSign system. To request paper copies from TRIO

To request delivery from us of paper copies of the notices and disclosures previously provided by us to you electronically, you must send us an e-mail to xxxxx.xxxxxxxxxxx@xxxxxxxxxxx.xxx and in the body of such request you must state your e-mail address, full name, US Postal address, and telephone number. We will bill you for any fees at that time, if any.

To withdraw your consent with TRIO

To inform us that you no longer want to receive future notices and disclosures in electronic format you may:

i. decline to sign a document from within your DocuSign session, and on the subsequent page, select the check-box indicating you wish to withdraw your consent, or you may;

ii. send us an e-mail to xxxxx.xxxxxxxxxxx@xxxxxxxxxxx.xxx and in the body of such request you must state your e-mail, full name, US Postal Address, and telephone number. We do not need any other information from you to withdraw consent.. The consequences of your withdrawing consent for online documents will be that transactions may take a longer time to process..

Required hardware and software

Operating Systems:	Windows® 2000, Windows® XP, Windows Vista®; Mac OS® X
Browsers:	Final release versions of Internet Explorer® 6.0 or above (Windows only); Mozilla Firefox 2.0 or above (Windows and Mac); Safari™ 3.0 or above (Mac only)
PDF Reader:	Acrobat® or similar software may be required to view and print PDF files
Screen Resolution:	800 x 600 minimum
Enabled Security Settings:	Allow per session cookies

** These minimum requirements are subject to change. If these requirements change, you will be asked to re-accept the disclosure. Pre-release (e.g. beta) versions of operating systems and browsers are not supported.

Acknowledging your access and consent to receive materials electronically

To confirm to us that you can access this information electronically, which will be similar to other electronic notices and disclosures that we will provide to you, please verify that you were able to read this electronic disclosure and that you also were able to print on paper or electronically save this page for your future reference and access or that you were able to e-mail this disclosure and consent to an address where you will be able to print on paper or save it for your future reference and access. Further, if you consent to receiving notices and disclosures exclusively in electronic format on the terms and conditions described above, please let us know by clicking the ‘I agree’ button below.

By checking the ‘I agree’ box, I confirm that:

• I can access and read this Electronic CONSENT TO ELECTRONIC RECEIPT OF ELECTRONIC CONSUMER DISCLOSURES document; and

• I can print on paper the disclosure or save or send the disclosure to a place where I can print it, for future reference and access; and

• Until or unless I notify TRIO as described above, I consent to receive from exclusively through electronic means all notices, disclosures, authorizations, acknowledgements, and other documents that are required to be provided or made available to me by TRIO during the course of my relationship with you.