A Phase 3, Randomized, Open Label Study to Compare Nivolumab plus Concurrent Chemoradiotherapy (CCRT) followed by Nivolumab plus Ipilimumab or Nivolumab plus CCRT Followed by Nivolumab vs CCRT followed by Durvalumab in Previously Untreated, Locally Advanced Non-small Cell Lung Cancer
- Conditions
- Lung cancernon small cell lung cancer10038666
- Registration Number
- NL-OMON52857
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
1) ECOG performance status <=1
2) Locally advanced stage IIIA, IIIB, or IIIC (T1-2 N2-3 M0, T3 N1-3 M0, or T4
N0-3 M0) pathologically-confirmed (including Cytology) NSCLC, according to 8th
TNM classification, that is amenable to definitive CCRT. Participants who are
not planned for potential curative surgical resection are eligible, except for
those foregoing surgery due to clinical contraindication for general
anesthesia/surgery. Participants must be evaluated by the site*s
multidisciplinary team (eg, medical oncologist, surgeon, radiologist) during
screening to assess the suitability of the participant for the study.
i) Overt cT4 disease. Vertebral invasive disease must not extend into the
spinal canal. OR
ii) Nodal status N2 or N3 must be proven (by biopsy in at least one N2 or N3
node, via EBUS, mediastinoscopy, or thoracoscopy) OR
iii) Nodal status N1 must be proven by biopsy in at least one N1 node, via
EBUS, mediastinoscopy or thoracoscopy for T3 disease, unless the lesion is
unamenable or the biopsy procedure is medically infeasible (must be documented
in the medical record)
Note: fine needle aspiration/cytology is acceptable for diagnosis and staging
purposes
3) Newly diagnosed and treatment-naïve, with no prior local or systemic
anticancer therapy given as primary therapy for locally advanced disease
4) Measurable disease per RECIST 1.1 criteria
5) All participants must have tissue submitted to a central laboratory during
screening, obtained within 3 months prior to enrollment. Biopsy should be
excisional, core needle or surgical specimen. Fine needle aspiration is
unacceptable for submission.
For entry into the maintenance therapy of the study, the below criteria must be
met:
1) Note: Inclusion Criteria 4 a) was removed as per Protocol Amendment 02. ECOG
performance status <=1
2) No BICR-confirmed progressive disease per RECIST 1.1 during or after CCRT
3) No current or prior use of immunosuppressive medication within 14 days
before the first dose of maintenance immunotherapy, with the exceptions of
intranasal and inhaled corticosteroids or systemic corticosteroids at
physiological doses, which are not to exceed 10 mg/day of daily prednisone
equivalent. Systemic steroid administration required as prophylaxis against or
to manage toxicities arising from CCRT is allowed
4) Any toxicity from CCRT should resolve to Grade 1 or baseline (except for
Grade 2 fatigue, esophagitis or alopecia).
5) Participants in Arm A and Arm B that received nivolumab should NOT meet
discontinuation criteria for immunotherapy (Section 8.1.1 of the protocol).
1) Any condition including medical, emotional, psychiatric, or logistical that,
in the opinion of the Investigator, would preclude the patient from adhering to
the protocol or would increase the risk associated with study participation or
study drug administration or interfere with the interpretation of safety
results (eg, a condition associated with diarrhea or acute diverticulitis)
2) Active infection requiring systemic therapy within 14 days prior to
randomization
3) Concurrent malignancy (present during screening) requiring treatment or
history of prior malignancy active within 2 years prior to randomization (ie.
participants with a history of prior malignancy are eligible if treatment was
completed at least 2 years before randomization and the participant has no
evidence of disease). Participants with history of prior early stage basal
/squamous cell skin cancer or non-invasive or in situ cancers that have
undergone definitive treatment at any time are also eligible.
4) Participants with an active, known or suspected autoimmune disease.
Participants with type I diabetes mellitus, hypothyroidism only requiring
hormone replacement, skin disorders(such as vitiligo, psoriasis, or alopecia)
not requiring systemic treatment, or conditions not expected to recur in the
absence of an external trigger are permitted to enroll
5) Participants with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of start of randomization. Inhaled
or topical steroids, and adrenal replacement steroid doses > 10 mg daily
prednisone equivalent, are permitted in the absence of active autoimmune disease
6) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4
antibody, or any other antibody or drug specifically targeting T-cell
co-stimulation or checkpoint pathways
7) Presence of pleural/pericardial effusion on CT scan and/or X-ray. Effusions
that are too small to be tapped safely are acceptable
8) Participants with EGFR mutation regardless of mutation type are excluded.
Non-squamous tumour with unknown EGFR mutation status must be tested for EGFR
mutation.
9) Known ALK translocation and/or ROS1 rearrangement
10) History of organ or tissue transplant that requires systemic use of immune
suppressive agents
11) Known history of positive test for human immunodeficiency virus (HIV) or
known
acquired immunodeficiency syndrome (AIDS).
12) Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection within 4 weeks prior to screening. Symptoms must have resolved and
based on investigator assessment in consultation with the medical monitor,
there are no sequelae that would place the participant at a higher risk of
receiving investigational treatment.
13) Prior/Concomitant Therapy
a) Prior thoracic radiotherapy. Exceptions are prior radiotherapies involving
the chest for clinical conditions other than lung cancers (eg, breast cancer)
of which the radiation field does not overlap with that of the disease under
study AND does not have FDG uptake at the previously irradiated area of the
lung per the PET scan performed during screening. All other prior radiotherapy
is allowed and must be completed at least 30 days prior to study treatment with
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoints are:<br /><br>* PFS by RECIST 1.1 per Blinded Independent Central Review (BICR) </p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary endpoints are:<br /><br>• OS for Arm A vs Arm C<br /><br>• PFS by RECIST 1.1 per BICR for Arm B vs Arm C<br /><br>• OS for Arm B vs Arm C<br /><br>• PFS by RECIST 1.1 per BICR for Arm A vs Arm B<br /><br>• OS for Arm A vs. Arm B<br /><br>• Objective Response Rate (ORR) by RECIST 1.1 per BICR<br /><br>• Duration of Response by RECIST 1.1 per BICR<br /><br>• Time to Response (TTR) by RECIST 1.1 per BICR<br /><br>• PFS by RECIST 1.1 per Investigator assessment<br /><br>• ORR by RECIST 1.1 per Investigator assessment<br /><br>• DoR by RECIST 1.1 per Investigator assessment<br /><br>• TTR by RECIST 1.1 per Investigator assessment<br /><br>• TTDM by RECIST 1.1 per Investigator assessment<br /><br>• Incidence of AEs, SAEs, and select AEs<br /><br>• Proportion of participants without meaningful symptom deterioration following<br /><br>48 weeks of maintenance therapy based on LCS subscale of FACT-L and NSCLC-SAQ</p><br>