FDA novel oncology drug approvals in 2025: Trends and strategic insights for developers

In 2025, the FDA sustained its strong momentum in advancing drug innovation, approving 58 new molecular entities and novel biologic drugs (46 by CDER, 12 by CBER), with about half designed for rare diseases^1,2. Oncology remains a leading therapeutic area for development of new drugs, comprising 28% of the 2025 new drug approvals (all by CDER, Table 1).  

Table 1. Novel oncology drugs approved by FDA in 2025

AA: Accelerated approval; BTD: Breakthrough therapy designation; Rand. Dose-Finding: Pre-marketing randomized dose-finding; Dose Opt. PMR: Post-marketing requirement (PMR) trial for dose optimization; ADC: Antibody-drug conjugate; BTCE: Bispecific T-Cell engager; LGSOC, Low grade serous ovarian cancer; NSCLC: Non-Small Cell Lung Cancer; MM: Multiple Myeloma; HR: Hormone receptor; ER: Estrogen Receptor; BCMA: B-cell maturation antigen; NF1: Neurofibromatosis Type 1; HSCT: Hematopoietic stem cell transplantation; TGCT: Tenosynovial giant cell tumor.

The 2025 novel oncology drug approvals reflect the following insights that are informative to sponsors of new cancer therapies^1,2,3,4.

Small molecules remain an important treatment modality

Despite the progressive growth of biologic therapies for oncologic diseases, with identification of new targets and pathways, there is still a role for novel small molecules. In 2025, small molecules accounted for 69% (11/16) of new oncology approvals. In comparison, biologic drug products (3 antibody drug conjugates (ADCs), 1 monoclonal antibody, and 1 bispecific T-cell engager) accounted for 31% (5/16) of new drug approvals (Figure 1). 

Figure 1. 2025 FDA novel oncology drug approvals, by modality (n=16)

The percentage of novel small molecule oncology drugs (69%) in 2025 is almost twice the average of 38% in the previous three years. This resurgence of highly selective small molecules highlights how structure‑guided drug design and mutation‑specific targeting led to approvals of additional effective therapies for non-small cell lung cancer (NSCLC) and acute myeloid leukemia (AML). For example, both Hernexeos^® and Hyrnuo^® offered new hope for HER2-Mutated NSCLC; Zegfrovy^® added a treatment option against notoriously difficult-to-treat NSCLC with EGFR Exon 20 insertion mutations; and Komzifti^® introduced a targeted oral option for NPM1-Mutant AML (Figure 2).

Figure 2. 2025 FDA novel oncology drug approvals, by tumor type (n=16)

NSCLC: non-small cell lung cancer; MM: Multiple Myeloma; AML: acute myeloid leukemia; LGSOC: Low-grade serous ovarian cancer; TGCT: Tenosynovial Giant Cell Tumor; NF1-PN: Neurofibromatosis type 1 plexiform neurofibromas, NPC: Nasopharyngeal carcinoma; HSCT-related: Hematopoietic stem-cell transplantation-related cancers. 

Most approved novel oncology drugs represent advancements in the clinical armamentarium

Many of the 16 approved novel oncology drugs had one or more expedited and other designations (Figure 3). These designations demonstrate the innovations occurring in oncology drug development, particularly for rare cancers, and reflect the FDA’s prioritization of innovative cancer therapies to address high unmet needs. 

Figure 3. 2025 FDA novel oncology drug approvals, regulatory features (n=16)

Response-based assessments are acceptable for accelerated or regular approvals of rare oncology indications

Among the 16 approved novel oncology drugs, 7 (44%) received accelerated approval and 9 (56%) received traditional approval. Primary efficacy endpoints such as overall response rate (ORR) or complete response (CR) were considered to provide robust response‑based evidence to support all 7 accelerated approvals and 4 of the 9 traditional approvals for rare oncology diseases (e.g., NF1‑PN, TGCT, HSCT, NPM1+ AML, ROS1+ NSCLC; See Table 1). This reflects the FDA’s willingness to accept robust response‑based evidence when randomized trials with progression-free survival (PFS) or overall survival (OS) as primary endpoints are impractical or unethical due to rarity of diseases - an important signal for orphan oncology drug developers. Among the 9 traditional approvals, only 3 (Datroway^®, Penpulimab-kcqx, Inluriyo^®) were based on PFS, and 2 (Grafapex^®, Blenrep^®) were based on OS.

Determining the optimal dose is mandatory 

The FDA has been embedding its principles of dose optimization into drug development through Project Optimus⁵ since 2021. Moving away from the ‘Maximum Tolerated Dose’ (MTD) model toward finding the ‘optimal dose’ is a significant paradigm shift in oncology drug development. Per Project Optimus, FDA expects model-informed drug development (MIDD) and a randomized dose-finding study for the determination of optimal dose.

The optimal dose should provide maximum efficacy with an acceptable safety profile for a specific indication. The proposed dosing regimen should be justified as ‘optimal’ based on integrated dose-exposure-response analyses by pooling all available clinical and nonclinical data. To determine whether a proposed dose is optimal, the FDA reviewers simply ask two questions: Could the dose go higher? Could the dose go lower? If the totality of evidence supports an answer of ‘no’ to both questions, the FDA accepts the proposed dose as the optimal dose for further development or approval. If not, the FDA may issue a post-marketing requirement (PMR) for dose optimization trial if the dose is not adequately justified as optimal. 

In 2025, the proposed doses of 9 (56%) drugs were accepted based on integrated dose-exposure-response analyses only. The doses for 4 (25%) approvals were determined by a randomized dose-finding trial in addition to integrated dose-exposure-response analyses. The 3 (19%) remaining approvals (Emrelis, Ibtrozi, Blenrep) had required post-marketing trials for further dose optimization. FDA issued a PMR for Emrelis to complete an ongoing randomized dose-finding trial with three dosing regimens. For Ibtrozi, FDA asked for testing a lower dosing regimen with meal, though not in a randomized manner, possibly due to the small patient population of ROS1+ NSCLC. For Blenrep, a PMR for randomized dose-finding trial was issued to test alternative dosing regimen with lower dose or longer dosing interval for better safety (particularly the ocular toxicity). 

Conclusions

Successful oncology development now depends on strategic alignment across three interconnected goals: target validation, disease selection, and dose optimization. In 2025, the oncology field saw a notable increase in small‑molecule approvals and a greater reliance on response rate as the primary efficacy endpoint for accelerated and regular approvals. Both trends are results of more rigorous target validation and smarter disease selection for drug development. Dose optimization has also become non‑negotiable. Under Project Optimus, randomized dose‑finding remains the FDA’s preferred approach to remove residual uncertainties in the dosing, though well‑integrated dose-exposure-response analyses can still support approval when patient populations are limited. Moving into 2026 and beyond, developers who anticipate and adapt to these regulatory expectations will be best positioned for success. 

With deep expertise in oncology drug development, our global Regulatory Consulting team – which includes ex-regulators from FDA and other major agencies - can optimize your regulatory strategy and streamline the path to bringing your innovative therapies to patients more efficiently and effectively.  

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References

1. Advancing Health Through Innovation: New Drug Therapy Approvals 2025 https://www.fda.gov/media/190705/download?attachment
2. 2025 Biological License Application Approvals. https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2025-biological-license-application-approvals
3. Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm 
4. Oncology (Cancer)/Hematologic Malignancies Approval Notifications https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications
5. FDA Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus 

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