US ORR-Based Oncology Approvals, DoR Under 6 Months: 2021–2026
For regulatory and clinical development teams, the choice of primary endpoint is among the most consequential decisions in oncology drug development. When overall response rate serves as the basis for accelerated or regular approval, the durability of that response becomes a critical dimension of the benefit-risk assessment — informing labeling negotiations, post-marketing commitments, payer coverage decisions, and the design of confirmatory trials. Understanding where the evidentiary bar has been set in recent agency decisions helps teams calibrate their own programs against current precedent.
This analysis examines US FDA oncology approvals and new-indication supplements decided between July 2021 and July 2026 in which a response-rate endpoint served as the primary efficacy basis, with specific focus on those cases where the median duration of response in the pivotal population fell below 6.0 months. The review draws on FDA approval letters, multidisciplinary review documents, and prescribing information to characterize the regulatory context, disease setting, and evidentiary standards associated with each qualifying approval event.
Want to ask Rhizome your own regulatory questions? Try it for free.
ORR-based US oncology approvals with a duration of response under 6 months (July 2021 to July 2026)
Bottom line
Among ORR-based US oncology approvals in the last five years, a median duration of response below 6 months is rare. The FDA's evidentiary bar for response-based (especially accelerated) approvals generally rests on responses being durable, so most of these approvals report a median DoR of 6 months or more, or a median that was not reached at data cutoff. In this window we identified one clear case of a response-rate-based oncology approval whose primary-population median DoR was under 6 months:
| Product | Active ingredient | Indication (approval type) | Approval date | ORR | Median DoR | Pivotal trial |
|---|---|---|---|---|---|---|
| KRAZATI + cetuximab | adagrasib | KRAS G12C-mutated locally advanced/metastatic colorectal cancer, after fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy (accelerated approval) | 2024-06-21 | 34% (95% CI 25, 45) | 5.8 months (95% CI 4.2, 7.6) | Study 849-001 (KRYSTAL-1) 1165 |
This was an extension of indication for adagrasib, which was first approved (also under accelerated approval, also on ORR and DoR) for KRAS G12C-mutated NSCLC in December 2022 11641165.
The one clear case: adagrasib (KRAZATI) plus cetuximab in KRAS G12C colorectal cancer
The colorectal indication was granted accelerated approval on June 21, 2024, in combination with cetuximab, based on objective response rate and duration of response from Study 849-001. FDA-confirmed figures are an ORR of 34% (95% CI 25, 45) with a median DoR of 5.8 months (95% CI 4.2 to 7.6 months) 1165. The label states the indication is approved under accelerated approval based on ORR and DoR, with continued approval contingent on verification of clinical benefit in confirmatory trials 1165. The 5.8-month median sits just under the 6-month line and is a reasonable illustration of a response-based approval where responses were real but comparatively short-lived, an acceptable trade-off given a heavily pretreated, biomarker-defined population with limited alternatives.
Why the list is so short: near-misses and the "not reached" pattern
Several response-rate-based approvals landed just above the 6-month threshold, which is why a strict reading yields so few qualifying products:
- Revumenib (REVUFORJ), relapsed/refractory KMT2A-translocated acute leukemia (2024-11-15): CR+CRh rate 21.2%, median DoR 6.46 months 1158.
- Mirvetuximab soravtansine (ELAHERE), FRα-positive platinum-resistant ovarian cancer (accelerated approval 2022): ORR 31.7%, median DoR 6.9 months 1172.
- Zenocutuzumab (BIZENGRI), NRG1 fusion-positive NSCLC (2024-12-04): ORR 33%, median DoR 7.4 months 1161.
More commonly, ORR-based approvals in this period reported durable responses well beyond 6 months, or a median that had not been reached at analysis:
- Tisotumab vedotin (TIVDAK), recurrent/metastatic cervical cancer (accelerated 2021): ORR 24%, median DoR 8.3 months (innovaTV 204) 1167.
- Talquetamab (TALVEY), relapsed/refractory multiple myeloma (accelerated 2023): ORR 73%, median DoR 9.5 months (MonumenTAL-1) 1163.
- Tarlatamab (IMDELLTRA), extensive-stage small cell lung cancer (accelerated 2024): ORR 40%, median DoR 9.7 months (DeLLphi-301) 1178.
- Trastuzumab deruxtecan (ENHERTU), HER2 IHC 3+ tissue-agnostic solid tumors (accelerated 2024): ORR 50%, median DoR 9.9 months (DESTINY-PanTumor02) 1174.
- Zongertinib (HERNEXEOS), HER2 (ERBB2)-mutant NSCLC (accelerated 2025): ORR 75%, median DoR 14.1 months (Beamion LUNG-1) 1171.
- Belzutifan (WELIREG), VHL disease-associated tumors (2021): median DoR not reached at analysis 1159.
The pattern is consistent: when FDA accepts response rate as the efficacy basis, the accompanying DoR is usually the reassurance that responses last. A sub-6-month median is the exception, not the rule.
Caveats and limitations for reviewers
- Reporting format varies. Many oncology labels report DoR as a range (for example "1.0+ to 12.3 months") or as the proportion of responders with DoR at or beyond a landmark (for example "76% with DoR ≥ 6 months") rather than a single median. Where the median was not reached or not estimable, the product was not counted as sub-6-month even if a fraction of responders had short-lived responses.
- Subgroups can be shorter. CNS, exploratory, and biomarker-subset analyses sometimes show shorter DoR than the pivotal population. These do not represent the basis of approval and were excluded.
- Legacy labels are not new approvals. Keyword screening also surfaced older drugs whose labels were merely revised in the window (for example a 2022 irinotecan/CAMPTOSAR label revision quoting a 5.8-month response duration from its 1990s colorectal data). These are neither new approvals nor new indications and were excluded.
- Coverage. This analysis is grounded in Drugs@FDA label and review text. Recall depends on how each label phrases its efficacy tables; a reader wanting an exhaustive, indication-by-indication audit (including every hematologic response-duration figure) can ask Rhizome to run a targeted per-product verification.