12 precedents matched · sorted by protocol similarity
96% match
KEYNOTE-189: Pembrolizumab + Chemo in Metastatic NSCLC
89% match
KEYNOTE-024: Pembrolizumab vs Platinum Chemo (PD-L1 ≥50%)
81% match
CHECKMATE-227: Nivolumab + Ipilimumab in Advanced NSCLC
74% match
EMPOWER-Lung 1: Cemiplimab Monotherapy in NSCLC
4.2 Eligibility Criteria
Adults (≥18 years) with histologically or cytologically confirmed non-small cell lung carcinoma (NSCLC) with stage IIIB–IV disease at screening, who have received no prior systemic therapy for advanced disease.
Participants must have an ECOG performance status of 0 or 1, and a tumor specimen with assessable PD-L1 expression status from a site-approved laboratory.
4.3 Exclusion Criteria
Participants with active, known, or suspected autoimmune disease. History of significant cardiovascular disease within 6 months. Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
5.1 Primary Endpoint
Progression-free survival (PFS) per RECIST v1.1 as assessed by Blinded Independent Central Review (BICR), defined as the time from randomization to first documented disease progression or death from any cause, whichever occurs first.
[ Continue drafting Section 5.2 — Secondary Endpoints… ]
7
Total findings
2
High risk · amendment
3
Patient burden flags
↓42%
vs. avg amendments
Eligibility Agent
2 warnings · review required
Age cutoff undefined for elderly subgroup (≥70). Missing stratification language per FDA 2021 guidance.
ref: KEYNOTE-189 §4.1 · FDA Guidance 2021-CGD-04
PD-L1 assay platform unspecified. Ambiguity flagged in 3 comparable IND submissions.
ref: NCT02578680, NCT02142738 amendment logs
Consistency Agent
1 critical · cross-section conflict
§4.3 exclusion "significant cardiovascular disease" conflicts with §8.2 Grade 3+ safety reporting definition.
ref: Internal cross-reference §4.3 ↔ §8.2
Primary endpoint (§5.1) BICR and RECIST v1.1 references complete and correctly versioned.
Patient Burden Agent
3 flags · burden score 62/100
22 total on-site visits across Cycles 1–4 exceeds precedent average of 16. High dropout risk in elderly subgroup.
ref: KEYNOTE-189 SoE · dropout analysis §14.2
Bone imaging required every cycle — consider Q2-cycle frequency per CHECKMATE-227 precedent.
ref: NCT02477826 SoE §9.9
Pregnancy test frequency (Q3W) exceeds FDA minimum guidance. Reducing to Q6W lowers burden without compliance risk.
ref: FDA Oncology Guidance 2020-R1 §4.3
Regulatory Agent
All checks passed
IND reference documents cited. FDA 2022 guidance on IO endpoint alignment incorporated.
ICH E6(R3) GCP requirements addressed. Risk-based monitoring language included.
EMA alignment checked. No divergence from EU CTR submission requirements identified.
Protocol history · ALAR-ONC-042
v2.4 — Eligibility & PD-L1 assay update
Agent review flagged 2 high-risk issues. §4.2 PD-L1 assay specification and elderly stratification require resolution before submission.
v2.3 — Schedule & follow-up interval
Long-term follow-up adjusted from Q8W to Q12W. LTFU endpoint windows updated. No regulatory impact assessed.
v2.2 — Primary endpoint clarification
BICR language added to §5.1 per FDA alignment. RECIST version number clarified.
Submission timeline
Precedent search
12 precedents identified
Protocol drafted
v2.3 approved, v2.4 in progress
Agent review
7 findings · 2 unresolved
Sponsor QA sign-off
Pending review completion
IND submission
Generated outputs · ALAR-ONC-042 · v2.4
Protocol synopsis
Structured 6-page synopsis with all key design decisions source-linked to precedent protocols and regulatory guidance.
14 sources cited
85%
Amendment risk report
Audit-ready report summarizing agent findings, risk scores, and recommended revisions with full source traceability.
7 findings
Ready
Informed consent draft
Plain-language ICF aligned to eligibility criteria and schedule of events. Readability grade 8.
Pending §4.2 fix
Blocked
Regulatory strategy memo
FDA Type B meeting preparation memo covering endpoint design, PD-L1 assay specification, and risk mitigation strategy.
Not generated
Generate ↗
Schedule of events
Full SoE table mapping all assessments, dosing, imaging, and labs across Screening, Cycle 1 & Cycle 2. Patient burden score: 62/100 — 3 optimization opportunities identified.
Ready · v2.4
View ↗