Your list of questions is really clever—my comments on the different pathways.
1) Accelerated Approval - Confirmatory trial- Label expansion for second- and third-line treatment in NSCLC:
- Hurdle: ResQ201A, as the confirmatory trial, raises questions: it involves two drugs, Anktiva and Tislelizumab. The key issues are which drug is responsible for the effect and the cost of both drugs.
- Anktiva would be more effective as a first-line treatment because, in second- and third-line therapies, the immune system is compromised, and Anktiva requires a base of NK and T cells to activate.
2) "Supportive Care" medications (like Epogen and Neupogen)
- Not likely. Three hurdles as mentioned: Endpoint, Dual-mechanism, and safety/risk
3) Tumor agnostic therapeutic indication ("failing chemo“)
- This is genius, and I hope IBRX will follow a similar pathway
Now I come up with another path Chat-GPT was proposing two days ago:
4) First-line approval pathway in NSCLC
09.09.25: Chat-GPT abstract
2024: Change in Quilt-2023 set-up:
Participant enrollment will only occur for Cohort D. Cohort D will evaluate the efficacy and safety of N-803 in combination with chemoimmunotherapy containing approved CPIs (nivolumab plus ipilimumab) as first-line treatment for participants with stage III or IV squamous or nonsquamous NSCLC.
First-line NSCLC (no formal FDA interaction)
- A press release in September 2024 did mention intentions to launch Phase 3 trials in 1st and 2nd-line NSCLC (ResQ301 and ResQ302) after success in 2nd/3rd line.
- However, there’s no indication these have reached the FDA in a formal IND or meeting request. The FDA engagement remains focused solely on later-line disease.
Question
| Answer
| Did FDA refuse first-line trial?
| No documented refusal. It appears ImmunityBio simply did not pursue it initially.
| Why no first-line design?
| Likely due to regulatory hurdles requiring large, randomized trials and less favorable cost-benefit at that stage.
| FDA requested data in 2nd/3rd-line?
| Yes—FDA engaged specifically to discuss registration plans in CPI-resistant NSCLC population.
|
Why this aligns with standard regulatory practice:
- Salvage (2nd/3rd-line) studies often allow single-arm designs with historical comparisons, especially in tumor types lacking effective options.
- First-line oncology increasingly demands randomized superiority trials against well-established SOC (e.g. pembrolizumab ± chemo), which are resource-intensive and higher-risk in regulatory review.
ResQ301 / ResQ302 – First-Line NSCLC Trials
- ResQ301 (1st-line) and ResQ302 (2nd-line) are mentioned in ImmunityBio’s 2024 QUILT-3.055 press release. The company states that QUILT-2.023 (a Phase 3 first-line trial) and ResQ trials have been activated across first- and second-line NSCLC. .
- A January 2025 analysis from Oncology Pipeline confirms planning for these trials:
- ResQ301 is intended for first-line NSCLC,
- ResQ302 for second-line,
- with ResQ201A already launched for CPI-resistant disease.
Despite the promise, clinicaltrials.gov does not yet list active studies under ResQ301/302, suggesting that these trials are still in development (pre-IND stage) and not yet open for enrollment.
Summary Table
Trial / Program
| Status & Notes
| ResQ201A
| Active, Phase 3 for CPI-resistant NSCLC.
| ResQ301 (1st-line)
| Mentioned in strategy; not yet active on trial registries.
| ResQ302 (2nd-line)
| Mentioned; likely in planning, but not active yet.
| QUILT-2.023
| Listed on company site as first-line Phase 3 program. Exact details pending.
| FDA Feedback
| Confirmed for 2nd/3rd-line; no public documentation regarding first-line trials.
| |
