Induction Chemo-Nivo in Unresectable Stage III NSCLC

Conditions

Lung Cancer, Nonsmall Cell, Lung Cancer Stage III

Keywords

Nivolumab, unresectable

Brief summary

The purpose of this study is to determine the response rate, safety, and effectiveness of a combination therapy in patients with lung cancer.

Michiel M. Smeenk, Judi N.A. van Diessen, Thierry N. Boellaard, Koen J. Hartemink, Jeltje F. de Vries et al. (11 authors)

Clinical Cancer Research2025-01-172 citations

10.1158/1078-0432.ccr-24-3476

Phase II study of induction platinum doublet in combination with nivolumab followed by surgery or concurrent chemotherapy-nivolumab-radiation in unresectable stage IIIA-C non-small cell lung cancer (NSCLC).

Ralph Zinner, Shari L. Meyerson, Ronald C. McGarry, Timothy W. Mullett, John L. Villano et al. (20 authors)

Journal of Clinical Oncology2024-06-01

10.1200/jco.2024.42.16_suppl.tps8122

Interventions

COMBINATION_PRODUCTNivolumab and Chemotherapy

3 cycles of the proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamous; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamous) will be administered then CT and biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks

DRUGNivolumab

Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation

PROCEDUREPost Induction Surgery

Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by surgery in patients whose tumors were unresectable stage IIIA-C at baseline on the basis of lymphadenopathy and are determined to be resectable after responding to induction chemotherapy-nivolumab. The participants have an option for post op XRT, then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles

RADIATIONPost Induction XRT

Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. The participants then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Chemo, biopsy, surgery with option for post op chemo or no surgery with concurrent chemo

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Squamous and non-squamous non-small cell lung cancer that is at baseline, unresectable stage IIIA-IIIC (8th edition AJCC) and not previously treated * PD-L1 level needs to be measured with values 0-100% eligible * EGFR/ALK/ROS1 Wild Type or unknown genetic alterations in these genes * ECOG Performance Status ≤ 1 * Adequate organ and marrow function * Adequate pulmonary reserve (e.g., FVC, FEV1, TLC, FRC, and DLCO) capable of tolerating the proposed lung resection * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Patients with a 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 * Clinical risk assessment of cardiac function using the New York Heart Association Functional Classification class 2B or better * Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

* Patients who have participated in a study with an investigational agent or device within 2 weeks of enrollment * Any prior radiotherapy to the lung * Any prior treatment for NSCLC * Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways * Any history of a severe hypersensitivity reaction to any monoclonal antibody * Any history of allergy to the study drug components * primary tumors involving the esophagus * pancoast tumors * Patients cannot have primary tumors which would remain unresectable * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab or other agents used in study * Any active or history of autoimmune disease (including any history of inflammatory bowel disease), or history of syndrome that required systemic steroids or immunosuppressive medications * Ongoing requirement for systemic corticosteroids greater than the equivalent of prednisone 10mg * previous malignancies * history of interstitial lung disease * Patients requiring continuous supplemental oxygen * Use of any live vaccines against infectious diseases (e.g., influenza, varicella. etc.) within 4 weeks (28 days) of initiation of study therapy * Active systemic infection requiring therapy * Patients with uncontrolled intercurrent illness * Patients with psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or lactating women

Design outcomes

Primary

Measure	Time frame	Description
Response Rate After Induction	9 weeks	post induction radiographic response by cat scan

Secondary

Measure	Time frame	Description
Percent of Participants Receiving Surgery	date of surgery, approximately 10 weeks	Rate of converting non-surgical stage III(A-C) to surgically resectable disease
Pathologic Complete Response (pCR)	post surgery, approximately 10 weeks	Number of participants with Pathologic Complete Response. Pathologic complete response (pCR) is defined by a surgical pathology specimen
Major Pathological Response (MPR)	post surgery, approximately 10 weeks	MPR rate, defined as number of participants with ≤ 10% residual tumor in lung and lymph nodes
Change in Toxicity	through study completion, up to 18 months	To assess safety, investigators will evaluate the rate of toxicity as defined by the Common Toxicity Criteria for Adverse Effects (CTCAE) scoring system.
Overall Survival (OS)	2 years	defined as the duration of time from start of treatment to time of death
Change in Patient-reported Quality of Life as Measured by FACT-TOI	through study completion, up to 18 months	patient-reported Quality of Life as measured by FACT-TOI (Functional Assessment of Cancer Therapy - Trial Outcome Index); defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS (lung cancer scale) scores obtained from 7-item questionnaires from the FACT-L (Version 4.0). Questions are on a 5-point scale from 0-4, where 0 = not at all and 4 = very much. Scores range from 0 to 84; higher score indicates better physical aspects of quality of life (QoL).
Progression Free Survival (PFS)	2 years	PFS is defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.

Countries

United States

Participant flow

Pre-assignment details

The study was terminated. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

Participants by arm

Arm	Count
Combination Chemotherapy and Nivolumab and Surgery Patients with lung cancer receiving combination therapy with surgery Nivolumab and Chemotherapy: 3 cycles of proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamous; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamous) administered then CT + biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks Nivolumab: Participants receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation Post Induction Surgery: Induction Chemo-NIVO x 3 cycles then CT + biopsy, followed by surgery in patients with unresectable stage IIIA-C tumors at baseline on the basis of lymphadenopathy and determined to be resectable after responding to induction chemotherapy-nivolumab. participants have an option for post op XRT, then NIVO at 480 mg IV every 4 weeks for 12 cycles Post Induction XRT: Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. Participants then receive NIVO at 480 mg IV every 4 weeks for 12 cycles.	0
Combination Chemotherapy and Nivolumab and Radiation Patients with lung cancer receiving combination therapy with radiation Nivolumab and Chemotherapy: 3 cycles of the proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamous; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamous) will be administered then CT and biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks Nivolumab: Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation Post Induction XRT: Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. The participants then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles.	0
Total	0

Baseline characteristics

Characteristic	—
Region of Enrollment United States	— participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 0
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	0 / 0	0 / 0

Outcome results

Primary

Response Rate After Induction

post induction radiographic response by cat scan

Time frame: 9 weeks

Population: he study was terminated. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

Secondary

Change in Patient-reported Quality of Life as Measured by FACT-TOI

patient-reported Quality of Life as measured by FACT-TOI (Functional Assessment of Cancer Therapy - Trial Outcome Index); defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS (lung cancer scale) scores obtained from 7-item questionnaires from the FACT-L (Version 4.0). Questions are on a 5-point scale from 0-4, where 0 = not at all and 4 = very much. Scores range from 0 to 84; higher score indicates better physical aspects of quality of life (QoL).

Time frame: through study completion, up to 18 months