Fostering Efficacy of Anti - PD-1 - Treatment: Nivolumab Plus Radiotherapy in Advanced NSCLC

NCT03044626 | Completed Phase 2

• 3 other identifiers: AIO-YMO/TRK-04152015-005741-31CA209-430
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 16

Brief Summary

AIO-YMO/TRK-0415 (FORCE) is a Phase 2, open-label of nivolumab, patients with metastatic non-squamous NSCLC with the necessity of radiotherapy of a metastatic site (e.g. bone) in 2nd-line or 3rd-line treatment for study group A and patients with metastatic non-squamous NSCLC without the necessity of radiotherapy in 2nd-line or 3rd-line treatment for study Group B.

Conditions

Carcinoma，Non-Small-Cell Lung; Metastatic Lung Cancer; Nonsmall Cell Lung Cancer; Lung Adenocarcinoma Metastatic; Large Cell Lung Carcinoma Metastatic

Keywords

Nivolumab; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR) according to RECIST 1.1 criteria

  through study completion, an average of 18 months

Secondary Outcomes (6)

• progression free survival (PFS)

  approx. 6 months

• PFS using assessment according to irRECIST

  approx. 6 months

• ORR using assessment according to irRECIST

  approx. 6 months

• Overall Survival (OS)

  approx. 57 months

• Adverse Events

  approx. 36 months

Other Outcomes (4)

• Radiation oncology endpoint: absolute size of gross tumor (GTV)

  approx. 57 months

• Radiation oncology endpoint: clinical target (CTV)

  approx. 57 months

• Radiation oncology endpoint: planning target volume (PTV)

  approx. 57 months

Study Arms (2)

study group A

EXPERIMENTAL

Patients with metastatic non-squamous NSCLC with the necessity of radiotherapy of a metastatic site (e.g. bone) in 2nd-line or 3rd-line treatment: Nivolumab 240 mg fixed dose (q2w). First dose followed by radiotherapy. Radiotherapy has to start at the latest 72 hours after nivolumab administration. Radiotherapy: A metastatic site will be treated with a radiation dose of 4 Gy for a total of 5 courses during a two week time interval (total dose 20 Gy)

Drug: Radiotherapy; Drug: Nivolumab

study group B

OTHER

Patients with metastatic non-squamous NSCLC without the necessity of radiotherapy in 2nd-line or 3rd-line treatment: Nivolumab 240 mg fixed dose (q2w).

Drug: Nivolumab

Interventions

Radiotherapy DRUG

Nivolumab 240 mg fixed dose (q2w). First dose followed by radiotherapy. Radiotherapy has to start at the latest 72 hours after nivolumab administration. Radiotherapy: A metastatic site will be treated with a radiation dose of 4 Gy for a total of 5 courses during a two week time interval (total dose 20 Gy)

study group A

Nivolumab DRUG

Nivolumab 240 mg fixed dose (q2w)

study group A; study group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• \. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• \. Age ≥ 18 years at time of study entry. 4. ECOG performance status 0-1. 5. Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) are eligible. For patients in group A, non-measurable and measurable lesions may be chosen for irradiation. However, in order to allow for evaluation of abscopal effects, patients in group A must have at least one measurable lesion beside the lesion planned to be irradiated. Lesions planned to be irradiated may not be defined as a measurable target lesion. Radiographic tumor assessment must be performed within 28 days before initiation of study treatment.
• \. Target Lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
• \. Patients with metastatic non-squamous non-small cell lung cancer in 2nd-line and 3rd-line treatment and
• no necessity of radiotherapy or
• the necessity of radiotherapy of a metastatic bone lesion or soft tissue lesion.
• Patients with intrathoracic metastases or intrathoracic progressive disease will be included if radiotherapy of the lung parenchyma is NOT required
• \. Patients who will receive study therapy after acceptable prior therapy as specified below are eligible: i. Patients who will receive study therapy as 2nd-line or 3rd-line of treatment:
• Patients must have experienced disease recurrence or progression during or after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease.
• First line therapy is defined as therapy used to treat advanced disease. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy. Subjects must have received at least 2 cycles of platinum doublet based chemotherapy before discontinuation for toxicity.
• Experimental therapies when given as separate regimen are considered as separate line of therapy.
• Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy and could comprise continuation of one or more of the agents used in the first-line therapy regimen or switch to another non cross-resistant agent. The initiation of maintenance therapy requires the lack of progressive disease with front-line therapy.
• Treatment given for locally advanced disease is not considered as a line of therapy for advanced disease. Subjects with recurrent disease \> 6 months after platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence, are eligible.
• Patients who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible.

You may not qualify if:

• Previous malignancy (other than NSCLC), which either progresses or requires active treatment.
• Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, endometrial, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required or anticipated to be required during the study period.
• Known activating EGFR mutation or a known ALK translocation.
• Prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents.
• Patients with interstitial lung disease.
• Any previous treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug.
• Patients should be excluded if they have an active, known or suspected autoimmune disease. NOTE: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. NOTE: Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Patients should be excluded if they are positively tested for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• History of severe hypersensitivity reactions to other monoclonal antibodies or any excipient.
• Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year)
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤14 days prior to the first dose of study treatment.
• Any other serious or uncontrolled medical disorder, active infection, physical examining, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject's ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Bristol-Myers Squibb: collaborator

Study Sites (16)

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

DRK Kliniken Berlin Mitte

Berlin, 13359, Germany

Location

Klinikum Chemnitz

Chemnitz, 09116, Germany

Location

Kliniken der Stadt Köln Krankenhaus Merheim

Cologne, 51109, Germany

Location

Universitätsklinikum Carl-Gustav-Carus

Dresden, 01307, Germany

Location

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730, Germany

Location

Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

Location

LungenClinic Grosshansdorf

Großhansdorf, 22927, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Universitätsklinikum des Saarlandes

Homburg/Saar, 66421, Germany

Location

Klinikverbund Kempten-Oberallgäu

Immenstadt im Allgäu, 87509, Germany

Location

Klinik Löwenstein

Löwenstein, 74245, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

Asklepios Fachkliniken München-Gauting

München-Gauting, 82131, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Related Publications (2)

• Bozorgmehr F, Chung I, Fischer JR, Bischof M, Atmaca A, Wetzel S, Faehling M, Bottke D, Wermke M, Troost EGC, Kropf-Sanchen C, Wiegel T, Schmidt B, Stupavsky A, Engel-Riedel W, Hammer-Hellmig M, Reinmuth N, Manapov F, Grohe C, Krempien R, Schumann C, Sterzing F, Reck M, Wurschmidt F, Fleckenstein J, Petroff A, Henschke S, Behnisch R, Cvetkovic J, Bruckner L, Schwab C, Stenzinger A, Gotze T, Kopp C, Schroder H, Debus J, Christopoulos P, Thomas M, Rieken S. Reconsidering palliative radiotherapy in addition to PD-1 blockade for non-small cell lung cancer: results from the FORCE phase II trial (AIO/YMO-TRK-0415). Clin Exp Metastasis. 2025 Jul 24;42(5):42. doi: 10.1007/s10585-025-10358-x.

  PMID: 40702361 DERIVED

• Bozorgmehr F, Hommertgen A, Krisam J, Lasitschka F, Kuon J, Maenz M, Huber PE, Konig L, Kieser M, Debus J, Thomas M, Rieken S. Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. BMC Cancer. 2019 Nov 8;19(1):1074. doi: 10.1186/s12885-019-6205-0.

  PMID: 31703637 DERIVED

Related Links

• AIO - Working Group for Medical Oncology from the German Cancer Society
• AIO-Studien-gGmbH

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Radiotherapy; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Farastuk Bozorgmehr, Dr.

  Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2017
• First Posted: February 7, 2017
• Study Start: February 10, 2017
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: January 13, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (16)