Radiotherapy to enhance the effects of an immune therapy before tumor surgery in patients with advanced non-small cell lung cancer (NSCLC). A multicenter phase II trial.

Start 31 Jul 2024 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 1 sites · Protocol SAKK 16/18

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ongoing, recruitment ended

Participants planned 90

Countries 1

Sites 1

Resectable, locally advanced non-small cell lung cancer (NSCLC, N2)

To evaluate whether the addition of immune-modulatory radiotherapy to standard neoadjuvant chemotherapy with cisplatin/docetaxel and peri-operative immunotherapy with the anti-PD-L1 antibody durvalumab in primarily resectable stage III(N2) NSCLC is efficacious and feasible.

Key facts

Sponsor: Swiss Group for Clinical Cancer Research
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Trial duration: 31 Jul 2024 → ongoing
Decision date (initial): 2024-04-17
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: AstraZeneca · SAKK

External identifiers

EU CT number: 2023-504536-18-00
WHO UTN: U1111-1291-2265
ClinicalTrials.gov: NCT04245514

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Secondary objectives 13

To determine if adding neoadjuvant immune-modulatory radiotherapy improves event-free survival (EFS)
To determine if adding neoadjuvant immune-modulatory radiotherapy improves recurrence free survival (RFS)
To determine if adding neoadjuvant immune-modulatory radiotherapy improves overall survival (OS)
To determine objective response (OR) after the end of neoadjuvant chemotherapy
To determine OR after neoadjuvant immunotherapy and immune-modulatory radiotherapy
To determine complete tumor regression with no evidence of vital tumor cells in the sections of the primary lesion and mediastinal lymph nodes after surgery
To determine if there’s presence of 10% or less of vital tumor cells in the sections of the primary lesion and/or mediastinal lymph nodes presenting focal microscopic disease after surgery
To determine if after the surgery the remaining node status of the patients according to the TNM cancer staging system is less than N2 (N0/1)
To determine complete resection rate (according to Rami-Porta R et al 2005)
To determine pattern of recurrence (loco-regional, distant)
To determine adverse events (AEs) and surgical complications
To determine delay in surgery
To determine postoperative 30-day mortality

Conditions and MedDRA coding

Resectable, locally advanced non-small cell lung cancer (NSCLC, N2)

Version	Level	Code	Term	System organ class
21.1	PT	10029519	Non-small cell lung cancer stage III	100000004864

Study design 9 periods

#	Title	Allocation	Blinding	Arms
1	Pre-Registration Informed consent and screening.	Not Applicable	None
2	Randomisation Randomisation via eCRF (day 0)	Randomised Controlled	None	A: 20x2 Gy radiotherapy (weekdaily, 4 weeks) B: 5x5 Gy radiotherapy (weekdaily, 1 week) C: 3x8 Gy radiotherapy (on alternate days, 1 week)
3	Neoadjuvant chemotherapy All subjects: Neoadjuvant chemotherapy with cisplatin and docetaxel: 3 cycles of 21 days. If adverse events (AEs) to cisplatin in cycle 1 or 2 preclude, the alternative is further use of carboplatin AUC 6. If AEs require to discontinue docetaxel, these chemotherapy regimes are permitted in cycle 2 and/or 3: pemetrexed 500 mg/m^2 or paclitaxel 200 mg/m^2 or vinorelbine 30 mg//m^2.	2	None
4	Neoadjuvant immune-modulatory radiotherapy According to randomisation: Radiotherapy, concurrent with neoadjuvant durvalumab immunotherapy (start corresponds to day 64 / week 10).	Not Applicable	None
5	Surgery All subjects: Between 4 and 6 weeks after the application of durvalumab (independent of the radiotherapy regimen).	2	None
6	Postoperative radiotherapy If indicated: Postoperative radiotherapy (start between 3 to 6 weeks after surgery). Postoperative RT is recommended for patients with R1/R2 resection, including patients with extracapsular spread of mediastinal lymph node metastases. For all other patients the use of postoperative RT is not permitted.	2	None
7	Adjuvant immunotherapy All subjects: Adjuvant immunotherapy with durvalumab: 13 cycles of 28 days	2	None
8	End of treatment All subjects: Within 1 month after last dose.	2	None
9	Follow up All subjects: year 1-2: every 3 months; year 3-5: every 6 months. Beyond year 5: every 6 months until end of treatment of the last patient.	2	None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

Histologically (cytology is accepted if histology is not possible) confirmed NSCLC (adeno-, squamous-, large cell carcinoma, or NSCLC not otherwise specified (NOS)) irrespective of genomic aberrations or PD-L1 expression status
Tumor stage T1-4>7 N2 M0 (i.e. T1-3 N2 or T4 N2 but T4 only allowed if due to size > 7cm, not allowed if due to invasion or nodule in different ipsilateral lobe), according to the TNM classification, 8th edition, December 2016. Mediastinal lymph node staging has to follow the process chart.
Age 18-75 years at time of registration
WHO performance status 0-1
Adequate organ function (incl. eGFR ≥ 60 mL/min)

Exclusion criteria 6

Presence of any distant metastasis or N3 disease. Brain metastases have to be excluded by CT or MRI
Sulcus superior tumors (Pancoast tumors) or T4 for any other reason than size >7cm
Any previous treatment for NSCLC
Any previous treatment with immune checkpoint inhibitors, including durvalumab
Previous radiotherapy to the chest (with the exception of tangential breast irradiation with minimal dose to lung and mediastinum, and superficial orthovoltage or electron irradiation of localized skin lesions)
Preexisting peripheral neuropathy (> Grade 1)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Event-free survival (EFS) at 12 months

Secondary endpoints 14

Event-free survival (EFS)
Recurrence-free survival (RFS) after R0 resection
Overall survival (OS)
Objective response (OR) after neoadjuvant chemotherapy
OR after neoadjuvant immunotherapy and immune-modulatory radiotherapy
Pathological complete response (pCR)
Local major pathological response (MPR)
Overall major pathological response (oMPR)
Rate of nodal down-staging to < ypN2
Complete resection rate
Pattern of recurrence (loco-regional, distant)
Adverse events (AEs) and surgical complications
Delay in surgery
Postoperative 30-day mortality

Investigational products

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

Test 1

IMFINZI 50 mg/mL concentrate for solution for infusion.

PRD6651398 · Product

Active substance: Durvalumab
Substance synonyms: MEDI4736
Pharmaceutical form: CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration: CONCENTRATE FOR SOLUTION FOR INFUSION
Max daily dose: 1500 mg milligram(s)
Max total dose: 21000 mg milligram(s)
Max treatment duration: 14 Day(s)
Authorisation status: Authorised
ATC code: L01XC28 — -
Marketing authorisation: EU/1/18/1322/001
MA holder: ASTRAZENECA AB
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Additional labelling

Auxiliary 7

Pemetrexed medac 100 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

PRD4296805 · Product

Active substance: Pemetrexed
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 500 mg/m2 milligram(s)/sq. meter
Max total dose: 1000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 2 Day(s)
Authorisation status: Authorised
ATC code: L01BA04 — -
Marketing authorisation: EU/1/15/1038/001
MA holder: MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL)
MA country: Liechtenstein
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Pemetrexed medac 500 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

PRD4296804 · Product

Active substance: Pemetrexed
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 500 mg/m2 milligram(s)/sq. meter
Max total dose: 1000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 2 Day(s)
Authorisation status: Authorised
ATC code: L01BA04 — -
Marketing authorisation: EU/1/15/1038/002
MA holder: MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL)
MA country: Liechtenstein
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatin Teva® 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung

PRD662245 · Product

Active substance: Cisplatin
Substance synonyms: Cis-diamminedichloroplatinum, (SP-4-2)-cis -diamminedichloroplatinum, CDDP
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: CONCENTRATE FOR SOLUTION FOR INFUSION
Max daily dose: 100 mg/m2 milligram(s)/sq. meter
Max total dose: 300 mg/m2 milligram(s)/sq. meter
Max treatment duration: 3 Day(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: 71983.00.00
MA holder: TEVA GMBH
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Doce onkovis 20 mg/ ml Konzentrat zur Herstellung einer Infusionslösung

PRD805679 · Product

Active substance: Docetaxel
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: CONCENTRATE FOR SOLUTION FOR INFUSION
Max daily dose: 85 mg/m2 milligram(s)/sq. meter
Max total dose: 255 mg/m2 milligram(s)/sq. meter
Max treatment duration: 3 Day(s)
Authorisation status: Authorised
ATC code: L01CD02 — DOCETAXEL
Marketing authorisation: 83325.00.00
MA holder: ONKOVIS GMBH
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Paclitaxel onkovis, 6 mg/ml, Konzentrat zur Herstellung einer Infusionslösung

PRD803002 · Product

Active substance: Paclitaxel
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 200 mg/m2 milligram(s)/sq. meter
Max total dose: 400 mg/m2 milligram(s)/sq. meter
Max treatment duration: 2 Day(s)
Authorisation status: Authorised
ATC code: L01CD01 — PACLITAXEL
Marketing authorisation: 77226.00.00
MA holder: ONKOVIS GMBH
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Carboplat onkovis 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung

PRD1808013 · Product

Active substance: Carboplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 400 mg/m2 milligram(s)/sq. meter
Max total dose: 800 mg/m2 milligram(s)/sq. meter
Max treatment duration: 2 Day(s)
Authorisation status: Authorised
ATC code: L01XA02 — CARBOPLATIN
Marketing authorisation: 86165.00.00
MA holder: ONKOVIS GMBH
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Vinorelbin onkovis 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung

PRD803004 · Product

Active substance: Vinorelbine Tartrate
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 30 mg/m2 milligram(s)/sq. meter
Max total dose: 120 mg/m2 milligram(s)/sq. meter
Max treatment duration: 4 Week(s)
Authorisation status: Authorised
ATC code: L01CA04 — VINORELBINE
Marketing authorisation: 87139.00.00
MA holder: ONKOVIS GMBH
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Swiss Group for Clinical Cancer Research

Sponsor organisation: Swiss Group for Clinical Cancer Research
Address: Effingerstrasse 33
City: Bern
Postcode: 3008
Country: Switzerland

Scientific contact point

Organisation: Swiss Group for Clinical Cancer Research
Contact name: Medical Advisor

Public contact point

Organisation: Swiss Group for Clinical Cancer Research
Contact name: Medical Advisor

Third parties 3

Organisation	City, country	Duties
Universitaetsspital Basel ORG-100030708	Basel, Switzerland	Laboratory analysis
CROLLL GmbH Auftragsforschungsinstitut (CRO) ORG-100033668	Oberasbach, Germany	On site monitoring, Code 12
Universitaetsspital Basel ORG-100030708	Basel Town, Switzerland	Laboratory analysis

Locations

1 EU/EEA country · 1 investigational sites

By country

Country	MS status	Planned subjects	Sites
Germany	Ongoing, recruitment ended	10	1
Rest of world Switzerland	—	80	—

Investigational sites

Germany

1 site · Ongoing, recruitment ended

Universitaetsklinikum Tuebingen AöR

Klinik für Radioonkologie, Otfried-Mueller-Strasse 10, Nordstadt, Tuebingen

Country notifications

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

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
Germany	2024-07-31		2025-03-25	2025-07-31

Results and documents

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

Documents 6 files

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

Type	Title	Version
Protocol (for publication)	D_Durvalumab TMG_statement	1
Protocol (for publication)	D_RT Manual_statement	1
Protocol (for publication)	D_SAKK 1618_Protocol_redacted	2.0
Protocol (for publication)	D_SAKK_1618_Germany-specific appendix_V1_2024-03-18_redacted	1.0
Summary of Product Characteristics (SmPC) (for publication)	E_Fachinfo_IMFINZI 50 mg-ml	2023-11
Synopsis of the protocol (for publication)	D_SAKK 1618_Trial synopsis	1

Application history

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

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-01-12	Germany	Acceptable 2024-04-16	2024-04-17
2	SUBSTANTIAL MODIFICATION	SM-3	2024-06-17	Germany	Acceptable	2024-08-15
3	NON SUBSTANTIAL MODIFICATION	NSM-1	2024-08-16	Germany	Acceptable 2024-04-16	2024-08-16
4	SUBSTANTIAL MODIFICATION	SM-4	2024-09-16	Germany	Acceptable 2024-10-15	2024-10-16
5	SUBSTANTIAL MODIFICATION	SM-5	2025-03-17	Germany	Acceptable 2025-04-14	2025-04-16
6	SUBSTANTIAL MODIFICATION	SM-6	2025-09-25	Germany	Acceptable 2025-10-20	2025-10-22