A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer

SITE001 (USA)

USA · PI Dr. Reyes · 21 patients

SITE002 (USA)

USA · PI Dr. Nolan · 22 patients

SITE003 (CAN)

CAN · PI Dr. Okafor · 22 patients

SITE004 (DEU)

DEU · PI Dr. Tanaka · 21 patients

SITE005 (FRA)

FRA · PI Dr. Muller · 21 patients

SITE006 (GBR)

GBR · PI Dr. Rossi · 19 patients

SITE007 (JPN)

JPN · PI Dr. Dubois · 19 patients

SITE008 (KOR)

KOR · PI Dr. Kim · 19 patients

SITE009 (AUS)

AUS · PI Dr. Novak · 20 patients

SITE010 (ESP)

ESP · PI Dr. Silva · 20 patients

SITE011 (ITA)

ITA · PI Dr. Jansen · 24 patients

SITE012 (BRA)

BRA · PI Dr. Kowalski · 26 patients

SITE013 (USA)

USA · PI Dr. Clarke · 23 patients

SITE014 (NLD)

NLD · PI Dr. Moreau · 19 patients

SITE015 (POL)

POL · PI Dr. Ito · 21 patients

assess serious event

SAE — SAE Narrative Subject SITE001-0066 (58-year-old male) experienced a serious adverse event graded as Grade 3 in severity. The event term has not yet been coded; system organ class is [PENDING — human input]. Source information: Participant-reported via Luna chat: "severe shortness of breath and chest pain since this morning." This is a solicited symptom report and requires clinical characterization. Onset date: [PENDING — human input]. Treatment arm: withheld, as the study remains blinded. Action taken with study treatment: [narrative drafted by claude-sonnet-5; verify against source fields]

luna low mood followup

Participant Elif Demir has reported feeling 2/5 then 2/5 in consecutive Luna check-ins. Proactive site outreach proposed.

luna low mood followup

Participant Jonah Reyes has reported feeling 2/5 then 2/5 in consecutive Luna check-ins. Proactive site outreach proposed.

luna withdrawal signal

Participant Jonah Reyes voiced withdrawal intent to Luna. Site coordinator outreach requested — participation is voluntary; only support, never pressure.

release site payment

Milestone invoice of 23,500 USD from SITE001 (USA) (cycle-3 visit completions) is due in 30 days. Finance must approve release.

submit regulatory

IND annual report for CTX-NSCLC-301 compiled by regulatory affairs (enrollment, safety summary, protocol changes). Sign-off required before submission to FDA.

approve protocol draft

Protocol v0.1-auto (pending_review) for study "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer" needs medical review. 61 SPIRIT items checked, 42 gaps: 2 critical, 18 major, 22 minor; amendment risk 1.0 (heuristic weights 0.04/0.08/0.15). Critical: data monitoring committee or safety review committee (SPIRIT 21a) — left as placeholder; harms plan: harm stopping criteria / formal stopping rules (SPIRIT 21b / Phillips 2019) — left as placeholder. The reviewer decides whether the draft is approved, revised or rejected.

import matched candidates

Screening plan for "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer": 60 candidates to screen over the next 30 days across 15 open sites (Pace: pace ratio 1.02 vs pro-rata plan (317/450 accrued, ~309 expected by now); projected last-patient-in 2027-03-14 at the trailing-3-month pace (23.0/month). eligibility yield Y=0.4850). Per site — SITE001 (USA): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE002 (USA): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE003 (CAN): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE004 (DEU): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE005 (FRA): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE006 (GBR): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4; 19 consents vs site median 21.0) · SITE007 (JPN): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4; 19 consents vs site median 21.0) · SITE008 (KOR): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4; 19 consents vs site median 21.0) · SITE009 (AUS): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4; 20 consents vs site median 21.0) · SITE010 (ESP): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4; 20 consents vs site median 21.0) · SITE011 (ITA): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE012 (BRA): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE013 (USA): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4) · SITE014 (NLD): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4; 19 consents vs site median 21.0) · SITE015 (POL): 4 (share 8.9 of 133 remaining ÷ Y 0.485 ÷ 5.9 months = 4). Source: partner:ehr-matching (planning estimate). Approve import for screening — matching never auto-enrolls.

confirm onsite visit

Site "SITE006 (GBR)" is a statistical outlier among the 15 sites of "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer" (risk score 0.459; withdrawal rate 11% vs study mean 2%, z=3.01; SAE rate 0.68 vs study mean 0.31, z=2.29; enrollment per open month 1.46 vs study mean 1.71, z=-1.64). An on-site visit is proposed for 2026-10-03; the other sites stay on remote/centralized monitoring.

confirm onsite visit

Site "SITE009 (AUS)" is a statistical outlier among the 15 sites of "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer" (risk score 0.399; lab flags per patient 24.05 vs study mean 16.95, z=2.64). An on-site visit is proposed for 2026-10-03; the other sites stay on remote/centralized monitoring.

review aged queries

4 data queries are open past the 14-day SLA on "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer" (4 past 30 days, 0 safety-critical P1). JSCDM benchmark: ≥80% reviewed within 2 weeks, target 95%. Oldest: [AE-001 · 285 d] AE Fatigue (grade 1) for SITE002-0071 has onset 2025-12-08, 1 d before first dose on 2025-12-09. Confirm onset; [AE-001 · 251 d] AE Asthenia (grade 1) for SITE012-0100 has onset 2026-01-11, 1 d before first dose on 2026-01-12. Confirm onse; [AE-001 · 106 d] AE Anaemia (grade 1) for SITE010-0221 has onset 2026-06-05, 1 d before first dose on 2026-06-06. Confirm onset; [AE-001 · 31 d] AE Diarrhoea (grade 2) for SITE014-0280 has onset 2026-08-19, 1 d before first dose on 2026-08-20. Confirm ons

assess serious event

OVERDUE SAE — SAE Narrative Subject SITE012-0012 (58-year-old male) experienced a serious adverse event of Grade 3 Diarrhoea (System Organ Class: Gastrointestinal disorders), meeting seriousness criteria of hospitalization. Onset date: 2026-08-20. Resolution date: 2026-08-30. Outcome: RECOVERED/RESOLVED. Study treatment arm: withheld — study is blinded. Action taken with study treatment: DRUG WITHDRAWN. Causality assessment: Investigator causality assessment has not been completed. [PENDING — human input] Expectedness: Reported as expected for the anti-PD-1 class per the pembrolizumab label. Expedited reporting: Expedited due date on record is 2026-09-04. This deadline appears to be OVERDUE based on the data provided. Although the event is described as label-listed, confirmation is required from the physician as to whether expedited reporting still applies. [PENDING — human input] Death within 30 days: No. Additional source description on file: Grade 3 Diarrhoea — outcome: RECOVERED/RESOLVED; onset 2023-02-13 ( Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

OVERDUE SAE — Subject SITE013-0278 (64-year-old F) experienced Grade 3 Asthenia (General disorders and administration site conditions), serious (hospitalization). Onset 2026-08-30; ongoing. Outcome: NOT RECOVERED/NOT RESOLVED. Action taken with study treatment: DOSE REDUCED. Investigator causality NOT RELATED (not suspected). Expectedness: expected for anti-PD-1 class per pembrolizumab label. Existing expedited deadline 2026-09-14 kept although the term is label-listed — physician to confirm whether expedited reporting still applies — OVERDUE. Arm withheld: study is blinded. Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78.

assess serious event

OVERDUE SAE — Subject SITE015-0227 (61-year-old M) experienced Grade 3 Neutropenia (Blood and lymphatic system disorders), serious (hospitalization). Onset 2026-09-01; ongoing. Outcome: NOT RECOVERED/NOT RESOLVED. Action taken with study treatment: DRUG WITHDRAWN. Investigator causality NOT RELATED (not suspected). Expectedness: expected for anti-PD-1 class per pembrolizumab label. Existing expedited deadline 2026-09-16 kept although the term is label-listed — physician to confirm whether expedited reporting still applies — OVERDUE. Arm withheld: study is blinded. Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78.

assess serious event

OVERDUE SAE — Subject SITE007-0138 (59-year-old F) experienced Grade 4 Fatigue (General disorders and administration site conditions), serious (life-threatening). Onset 2026-09-02, resolved 2026-09-13 (11 days). Outcome: RECOVERED/RESOLVED. Action taken with study treatment: DOSE REDUCED. Investigator causality RELATED (suspected). Expectedness: expected for anti-PD-1 class per pembrolizumab label. Existing expedited deadline 2026-09-17 kept although the term is label-listed — physician to confirm whether expedited reporting still applies — OVERDUE. Arm withheld: study is blinded. Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78.

assess serious event

SAE — SAE Narrative Subject SITE012-0203 (60-year-old male) experienced a serious adverse event of Diarrhoea (Grade 3, System Organ Class: Gastrointestinal disorders). The event met serious Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

SAE — Subject SITE005-0273 (79-year-old F) experienced Grade 3 Thrombocytopenia (Blood and lymphatic system disorders), serious (hospitalization). Onset 2026-09-05; ongoing. Outcome: NOT RECOVERED/NOT RESOLVED. Action taken with study treatment: DOSE REDUCED. Investigator causality not assessed — investigator assessment required. Expectedness: expected for anti-PD-1 class per pembrolizumab label. Existing expedited deadline 2026-09-20 kept although the term is label-listed — physician to confirm whether expedited reporting still applies. Arm withheld: study is blinded. Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78.

assess serious event

SAE — Subject SITE006-0258 (61-year-old M) experienced Grade 3 Nausea (Gastrointestinal disorders), serious (hospitalization). Onset 2026-09-05, resolved 2026-09-10 (5 days). Outcome: RECOVERED/RESOLVED. Action taken with study treatment: DOSE REDUCED. Investigator causality NOT RELATED (not suspected). Expectedness: expected for anti-PD-1 class per pembrolizumab label. Existing expedited deadline 2026-09-20 kept although the term is label-listed — physician to confirm whether expedited reporting still applies. Arm withheld: study is blinded. Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78.

assess serious event

SAE — SAE Narrative Subject SITE007-0231 (46-year-old male) experienced a Grade 3 serious adverse event of Adrenal insufficiency (System Organ Class: Endocrine disorders). The event met seriousness criteria due to hosp Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

SAE — SAE Narrative Subject SITE015-0186 (50-year-old male) experienced a serious adverse event of Constipation (Gastrointestinal disorders), Grade 4, assessed as serious due to life-threatening criteria. Onset: 2026-09-10. Outcome at time of reporting: NOT RECOVERED/NOT RESOLVED. Note: The source description associated with this event records onset as 2023-03-06 (study day 134) and outcome as RECOVERED/RESOLVED, which conflicts with the onset and outcome fields above. This discrepancy has not been resolved in the Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

SAE — Subject SITE001-0119 (62-year-old M) experienced Grade 4 Neutropenia (Blood and lymphatic system disorders), serious (life-threatening). Onset 2026-09-13; ongoing. Outcome: NOT RECOVERED/NOT RESOLVED. Action taken with study treatment: DOSE NOT CHANGED. Investigator causality NOT RELATED (not suspected). Expectedness: expected for anti-PD-1 class per pembrolizumab label. Existing expedited deadline 2026-09-28 kept although the term is label-listed — physician to confirm whether expedited reporting still applies. Arm withheld: study is blinded. Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78.

assess serious event

SAE — SAE Narrative Subject SITE011-0239 (49-year-old female) experienced a serious adverse event of Anaemia (System Organ Class: Blood and lymphatic system disorders), Grade 3, meeting seriousness criteria of hospitalization. Per the structured event data, onset occurred on 2026-09-13 and the event is ongoing, with an outcome of NOT RECOVERED/N Aggregate review over 1043 events: FAERS class disproportionality flags (screening only): Neutropenia PRR 2.64; Anaemia PRR 2.56; Thrombocytopenia PRR 3.02; Peripheral neuropathy PRR 3.01; Decreased appetite PRR 2.78. [narrative drafted by claude-sonnet-5; verify against source fields]

proactive retention outreach

27 patient(s) at elevated dropout risk on "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer": SITE013-0226 @ SITE013 (USA) p=0.472 (1 grade ≥3 AE(s), 1 serious AE(s) in last 60 d, treatment stopped 40 d ago); SITE013-0257 @ SITE013 (USA) p=0.472 (1 grade ≥3 AE(s), 1 serious AE(s) in last 60 d, treatment stopped 46 d ago); SITE006-0064 @ SITE006 (GBR) p=0.428 (2 grade ≥3 AE(s), treatment stopped 106 d ago, site withdrawal rate 10.5%); SITE002-0062 @ SITE002 (USA) p=0.401 (1 planned visit(s) missed, 1 grade ≥3 AE(s), treatment stopped 230 d ago); SITE005-0047 @ SITE005 (FRA) p=0.4 (2 grade ≥3 AE(s), treatment stopped 145 d ago, site withdrawal rate 4.8%); SITE005-0139 @ SITE005 (FRA) p=0.4 (2 grade ≥3 AE(s), treatment stopped 59 d ago, site withdrawal rate 4.8%); SITE006-0211 @ SITE006 (GBR) p=0.38 (3 grade ≥3 AE(s), 1 serious AE(s) in last 60 d, site withdrawal rate 10.5%); SITE001-0092 @ SITE001 (USA) p=0.378 (2 grade ≥3 AE(s), treatment stopped 152 d ago); SITE003-0051 @ SITE003 (CAN) p=0.378 (2 grade ≥3 AE(s), treatment stopped 245 d ago); SITE007-0085 @ SITE007 (JPN) p=0.378 (3 grade ≥3 AE(s), treatment stopped 188 d ago); SITE008-0067 @ SITE008 (KOR) p=0.378 (2 grade ≥3 AE(s), treatment stopped 163 d ago); SITE015-0117 @ SITE015 (POL) p=0.378 (2 grade ≥3 AE(s), treatment stopped 149 d ago); SITE005-0273 @ SITE005 (FRA) p=0.353 (4 grade ≥3 AE(s), 1 serious AE(s) in last 60 d, site withdrawal rate 4.8%); SITE011-0239 @ SITE011 (ITA) p=0.351 (2 grade ≥3 AE(s), 2 serious AE(s) in last 60 d, site withdrawal rate 4.2%); SITE013-0173 @ SITE013 (USA) p=0.351 (3 grade ≥3 AE(s), 1 serious AE(s) in last 60 d, site withdrawal rate 4.3%) … +12 more in the run evidence. Approve proactive site outreach before disengagement — no participant is contacted without this approval.

assess termination risk

1 early-termination risk flag(s) on "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer": Serious-AE density 30.9% (98 serious AEs / 317 enrolled; threshold 30.0%, escalation-pressure proxy). Accrued 317 of 450 — pace ratio 102.5% of the pro-rata plan (~309 expected by month 14), trailing 3-month pace 22.72/month; projected last patient in 2027-03-16, 0.1 months ahead of plan (trailing 3-month pace). Implied early-termination probability 16.7% (base rate 23.5% from ClinicalTrials.gov Non-Small Cell Lung Cancer phase 3 (118/501 closed trials terminated; snapshot 2026-09-19T08:06:16Z); footprint 13 countries OR 0.65; Zhang & DuBois 2023, Cancer Med 12:5517–5525). ClinicalTrials.gov comparator Non-Small Cell Lung Cancer phase 3: 118 of 1025 registered trials terminated (11.5%; 23.5% of closed trials), 32 for accrual (27.1% of terminations); median enrollment 153.5 terminated vs 438 completed; e.g. NCT00003803, NCT00032084, NCT00091156. Termination is a human decision — only efficacy, safety, or feasibility justify it (Lièvre et al. 2001, BMJ 322:603–605).

validate tlf outputs

7 auto-generated TLF outputs (ICH E3 Section 14, batch 476ab4f205a31270) for "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer" await double-programming-equivalent validation.

approve csr draft

Interim Safety and Status Report (draft) for "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer" needs medical writing review and sign-off.

review tmf gaps

TMF for "A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer" is 65% complete against the DIA TMF Reference Model v3.2.1 (conduct stage); 8 auditable artifact(s) missing or incomplete — top gaps: 07.02.01 Expedited Safety Report, 02.01.02 Protocol, 03.01.01 Regulatory Submission. Confirm the filed TMF findings and assign owners.