Here is a Chat GPT5 commentary summarizing, analyzing and explaining that data mannamal posted from the Abstract:
Here’s a straight read of what you sent, plus where it fits in the bigger picture for ImmunityBio (IBRX) and ANKTIVA/NAI.
What the figure shows (plain English) - Patients: previously treated NSCLC (non-small cell lung cancer) who relapsed after chemo-immunotherapy (checkpoint inhibitor ± chemotherapy).
- Treatment on study: keep the same CPI the patient already failed, and add NAI (nogapendekin alfa inbakicept; ANKTIVA). This is QUILT-3.055, a phase 2b, multicohort, open-label study. ImmunityBio
- The green curve (“Lymphocytes Maintained, ALC =1,500/µL”) shows median overall survival (OS) 21.1 months (95% CI 13.9–42.1).
The purple curve (“Severe Lymphopenia, ALC <1,200/µL”) shows median OS 11.5 months (95% CI 4.2–13.3).
The comparison they report is HR 0.33 (0.16–0.65), p=0.0009, favoring patients whose lymphocyte counts stayed high on therapy. (These are within-study subgroups; not randomized.) These exact numbers match the WCLC-2025 abstract summary. Larvol Delta
- The small inset (“Historical control: docetaxel 5–7 mo OS”) is there for context, pulling from older second-line docetaxel trials; modern post-IO standards (e.g., docetaxel + ramucirumab) typically show OS ~10–11 mo. So the 21-mo signal looks favorable, but cross-trial comparisons are not dispositive. PubMed Nature PMC
Trial basics you asked for - Indication: NSCLC after acquired resistance to checkpoint inhibitors (CPI); patients had progressed on the same CPI they then continued with NAI added. ImmunityBio
- Stage: Phase 2b (exploratory, non-randomized). ir.immunitybio.com
- Where conducted: Multicenter, primarily U.S.; presented by MUSC’s John Wrangle at WCLC 2024. (ClinicalTrials.gov lists QUILT-3.055 as a U.S. multi-center, open-label trial.) ImmunityBio ClinicalTrials.gov
- How far from approval in NSCLC: A confirmatory randomized phase 3 has been announced/initiated (ResQ program; one version pairs NAI with tislelizumab globally, target ~462 pts). There is no FDA approval for NSCLC yet; approval would generally require a positive phase 3 readout and subsequent regulatory review. ImmunityBio lungcancerstoday.com
What is NAI (a.k.a. ANKTIVA, N-803 / formerly ALT-803)? - Drug/class: a long-acting IL-15 receptor agonist “superagonist” complex that expands NK cells and CD8+ T cells (and memory T cells). Brand: ANKTIVA; code name N-803; older code ALT-803. Owner/developer: ImmunityBio (via its 2017 acquisition of Altor BioScience). U.S. Food and Drug Administration PMC MarketScreener
- What’s already approved: In April 2024, the FDA approved ANKTIVA + BCG for BCG-unresponsive NMIBC (CIS ± papillary)—bladder cancer, not lung. (Altor BioScience LLC is the BLA holder entity within the group.) U.S. Food and Drug Administration
How the abstract’s ALC analysis works (the jargon) - ALC (Absolute Lymphocyte Count): the number of lymphocytes per microliter in the CBC differential.
- ALC “median cutoff” / thresholds: The poster slices the cohort by pre-specified ALC thresholds (e.g., =1,500/µL versus <1,200/µL) and plots separate Kaplan–Meier OS curves.
- Lymphopenia: low lymphocyte count; here “severe” defined as ALC <1,000–1,200/µL (they analyze both <1,000 and <1,200 in text/figure).
- Hazard Ratio (HR): relative risk of death; HR 0.33 means the “ALC-maintained” group died at ~one-third the rate of the severely lymphopenic group over time (non-randomized comparison).
- P value 0.0009: log-rank test for the between-curve difference; statistically significant under conventional thresholds.
- “LSA” (lymphocyte-stimulating agent): their term for NAI’s role—pharmacologically reversing lymphopenia to “rescue” CPI activity. They’re positioning ALC as an actionable biomarker (akin to how ANC is used for neutropenia). Note: FDA has authorized an Expanded Access protocol for treating lymphopenia with ANKTIVA in solid tumors, but that’s not a label expansion. ImmunityBio
What the full phase 2 dataset looks like - QUILT-3.055 NSCLC cohort (n=86, 2L/3L+): median OS ~14.1–14.3 months in the all-comers, with survival out to ~58 months for some patients; 57% alive at 12 months in the 2024 WCLC presentation. The abstract you pasted then shows the ALC-maintained subgroup with median OS 21.1 months and a strong HR versus the lymphopenic subgroup. This suggests the immune-restorative hypothesis may matter clinically. (Again, it’s not randomized; prognostic enrichment and treatment effect are intermingled.) ImmunityBio Larvol Delta
How close is this to being practice-changing? - Regulatory status in NSCLC: Still investigational. ImmunityBio has announced/initiated randomized, global phase 3 trials of NAI + CPI vs standard of care in 2L/3L NSCLC (and first-line programs), but no phase 3 NSCLC readout yet and no lung-cancer label. Until a positive phase 3 and regulatory review, this is not approvable evidence. ImmunityBio lungcancerstoday.com
- Why the historical controls on the slide are risky: The figure cites early-2000s docetaxel data (5–7 mo). In the post-IO era, docetaxel + ramucirumab often yields OS around 10–11 months, narrowing the gap—and only a randomized comparison can separate prognosis (patients with higher ALC tend to be fitter) from true drug effect. PMC
Why the stock can struggle despite eye-catching curves - Evidence bar not yet cleared for NSCLC. The centerpiece is phase 2b, open-label, with post-hoc ALC stratification. Investors typically wait for randomized phase 3 proof. ir.immunitybio.com
- Regulatory setbacks elsewhere. In May 2025, FDA issued a Refusal-to-File for the sBLA seeking to expand ANKTIVA’s bladder label to papillary-only disease without CIS—reminding the market that regulatory risk remains. Cancer Network
- Commercial ramp vs. valuation. ANKTIVA bladder-cancer sales are growing but still small in absolute dollars (e.g., $26.4M Q2’25; $43M YTD at mid-2025). For a multi-billion valuation, the Street wants clearer visibility to large new indications (like NSCLC) or bigger quarterly revenue. ImmunityBio ir.immunitybio.com
- Balance-sheet worries (periodic). Through 2024–early 2025, commentary often flagged cash burn and financing needs, which pressure sentiment until operating cash-flows improve. Seeking Alpha
- Mechanism acceptance gap. The idea of treating lymphopenia as a therapeutic target (like G-CSF for neutropenia) is new in solid tumors; FDA did clear Expanded Access for “cancer BioShield” lymphopenia treatment, but broad adoption—and payer behavior—will depend on prospective data tying ALC correction to hard outcomes. ImmunityBio
Who owns NAI and what else it’s called - Nogapendekin alfa inbakicept (NAI) = ANKTIVA® (brand) = N-803 (current code) = ALT-803 (legacy code). Originated at Altor BioScience; acquired by NantCell/ImmunityBio (Patrick Soon-Shiong). Current approval: BCG-unresponsive NMIBC (CIS ± papillary). U.S. Food and Drug Administration Fierce Biotech
Quick glossary of the other terms on the slide - OS: Overall survival (time from treatment start to death from any cause).
- HR (hazard ratio): relative risk over the whole follow-up; <1 favors the numerator group.
- P value: probability the observed difference is due to chance under the null.
- CPI: checkpoint inhibitor (e.g., pembrolizumab or nivolumab).
- ALC =1,500 / <1,200: cutoffs used to define “lymphocytes maintained” vs “severe lymphopenia” groups.
- Kaplan–Meier curve: standard survival plot; the “At risk” row shows how many patients remain under observation at each time point.
Bottom line - The figure shows a compelling correlation: patients whose lymphocyte counts are maintained on NAI + the same CPI they’d failed lived substantially longer than those who stayed lymphopenic. That supports the immune-rescue hypothesis and justifies phase 3. But it is not yet registrational evidence for NSCLC. Approval in lung cancer will hinge on randomized phase 3 results now being organized (ResQ). Meanwhile, IBRX’s share price reflects (i) the non-registrational nature of the NSCLC data so far, (ii) regulatory hiccups on bladder-label expansion, and (iii) the early stage of commercial scaling vs. expectations. ImmunityBio+1 lungcancerstoday.com Cancer Network
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