Will the FDA approve ivonescimab in combination with chemotherapy in EGFR-mutated NSCLC after failure of a tyrosine kinase inhibitor?
deadline 2026-11-30
confidence medium
tier 2 evidence
49%Asturna estimate
Resolution criterion
Yes if the FDA publishes an approval (Drugs@FDA or a Summit Therapeutics release) no later than 30 November 2026. A complete response letter, a postponement of the PDUFA date, or the absence of a decision count as no. A label restricted to a subgroup that does not cover this combination and population (e.g. non-squamous histology only) counts as no; flag for manual review if the approved label's exact scope is unclear.
Verified starting state
BLA accepted, PDUFA date 14 November 2026. The interim progression-free survival analysis of HARMONi-3 (squamous cohort) did not meet its pre-specified significance threshold. Updated overall survival from HARMONi showed an HR of 0.76 in Western patients, not statistically significant. (July 2026)
What pushes it up
- BLA is accepted with an active PDUFA date of 14 November 2026, which falls before the 30 November 2026 deadline [tier 1].
- Updated overall survival from HARMONi demonstrated a favorable hazard ratio trend of 0.76 in Western patients [tier 1].
- Strong ongoing industry validation and investment surrounding ivonescimab and the PD-1xVEGF class [tier 2].
What pushes it down
- The updated OS HR of 0.76 in Western patients was not statistically significant, raising potential FDA scrutiny regarding applicability to the US population and adequacy of benefit [tier 1].
- HARMONi-3 interim progression-free survival in the squamous cohort failed to meet its pre-specified significance threshold, increasing regulatory caution [tier 1].
- Any standard 3-month review extension beyond the 14 November 2026 PDUFA date would push the decision past the 30 November 2026 deadline, resolving the question as No [tier 1].
What would move this number most
Whether the FDA accepts the non-statistically significant Western subgroup OS data from HARMONi without issuing a complete response letter or requesting a major amendment that extends the PDUFA date beyond 30 November 2026.
How this number is built
| Deadline | 2026-11-30 |
| Base rate | 73% |
| Best evidence | tier 2 · 3 article(s) used |
| Independent runs | 48 · 50 (spread 2 pts) |
| Confidence | medium |
| Evidence cap | not triggered |
| Last revised | 2026-10-10 20:00 |
| Model | gemini-3.8-flash |
Sources consulted
Probability history
2026-10-10 20:00 49% 70 article(s) on file · gemini-3.8-flash
- What pushes it up. BLA is accepted with an active PDUFA date of 14 November 2026, which falls before the 30 November 2026 deadline [tier 1].
- What pushes it up. Updated overall survival from HARMONi demonstrated a favorable hazard ratio trend of 0.76 in Western patients [tier 1].
- What pushes it up. Strong ongoing industry validation and investment surrounding ivonescimab and the PD-1xVEGF class [tier 2].
- What pushes it down. The updated OS HR of 0.76 in Western patients was not statistically significant, raising potential FDA scrutiny regarding applicability to the US population and adequacy of benefit [tier 1].
- What pushes it down. HARMONi-3 interim progression-free survival in the squamous cohort failed to meet its pre-specified significance threshold, increasing regulatory caution [tier 1].
- What pushes it down. Any standard 3-month review extension beyond the 14 November 2026 PDUFA date would push the decision past the 30 November 2026 deadline, resolving the question as No [tier 1].
- What would move this number most. Whether the FDA accepts the non-statistically significant Western subgroup OS data from HARMONi without issuing a complete response letter or requesting a major amendment that extends the PDUFA date beyond 30 November 2026.
2026-09-22 22:15 52% 6 article(s) on file · gemini-3.7-flash
Reasons not recorded for this revision (detailed history has only been kept since recently).
2026-09-21 23:10 70% 6 article(s) on file · openai/gpt-oss-120b (Groq)
Reasons not recorded for this revision (detailed history has only been kept since recently).
2026-09-21 22:17 44% 6 article(s) on file · gemini-3.5-flash
Reasons not recorded for this revision (detailed history has only been kept since recently).
2026-09-21 22:13 55% 6 article(s) on file · gemini-3.7-flash
Reasons not recorded for this revision (detailed history has only been kept since recently).
2026-09-19 07:32 70% 5 article(s) on file · gemini-3-flash-preview
Reasons not recorded for this revision (detailed history has only been kept since recently).