A new year is upon us and—per our tradition here at Blue Matter—it is time once again to explore the state of the oncology market. Oncology continues to be a dynamic therapy area, with significant ongoing research and new developments on what seems like a daily basis.
You may recall that last February, we published our 2025 Oncology Market Outlook. In that paper, we identified four key trends that we thought would drive the oncology market and generate the most interest throughout the year. Those trends were:
- Bi-specific antibodies will lead to an immuno-oncology (IO) renaissance in solid tumors – While showing solid results in liquid tumors, IO therapies had shown only limited utility in solid tumors. Nevertheless, we saw reasons for optimism and given all that was going on in early 2025, we predicted a virtual explosion of promising data from bi-specifics in solid tumors during the year.
- Synthetic lethality will come into focus – For 2025, we expected a proliferation of interest in synthetic lethality and synthetic lethal drug approaches, with a specific focus on work being done by IDEAYA Biosciences, REPARE Therapeutics, and several other companies.
- Degraders will further mature as a class – We predicted that 2025 would bring an explosion of interest in targeted protein degraders in oncology (and potentially beyond), with numerous important data readouts and new pivotal trial initiations during 2025.
- Cancer cachexia will attract a lot of attention – This complex, cancer-related wasting syndrome occurs in up to 80% of patients with advanced cancer. Given the high unmet need, we predicted that a lot of attention and investment dollars would be focused on cachexia throughout the year.
So, how did we do? Were our predictions for 2025 on point or were they far out in left field? Below, let’s revisit each one and explore them in a bit more detail.
Prediction 1 – Bi-specific antibodies will lead to an immuno-oncology (IO) renaissance in solid tumors
Last year, in our 2025 outlook, we noted that IO / cancer immunotherapy-based approaches had been facing significant challenges in solid tumors. Nevertheless, we identified a number of bright spots and predicted that bi-specific antibodies would usher in an IO “renaissance” in solid tumors. Below, we summarize some key developments and “takeaways” from this space in 2025.
PD‑1 anchored bispecifics emerged as the next IO backbone:
Summit Therapeutics’ ivonescimab (PD‑1×VEGF) reduced the risk of progression or death by ~40% versus tislelizumab + chemotherapy in first‑line squamous NSCLC, with a ~4‑month improvement in progression-free survival (PFS) and encouraging activity in unresectable hepatocellular carcinoma (HCC), prompting Summit to pursue a US filing.
Innovent Biologics’ IBI363 (PD‑1/IL‑2α fusion) delivered durable responses and survival in IO‑resistant melanoma and squamous NSCLC and secured a global co‑development / US co‑commercialization partnership with Takeda.
Next-generation dual checkpoint blockade is maturing with MacroGenics’ lorigerlimab (PD-1×CTLA-4). Utilizing the DART® platform, it is designed to intensify CTLA-4 blockade specifically on dual-expressing TILs, aiming to replicate the efficacy of Opdivo + Yervoy without the systemic toxicity. Development expanded in 2025 with the LINNET Phase 2 study in platinum-resistant ovarian cancer, while “pivotal signal” from the randomized LORIKEET study in mCRPC are awaited to determine the asset’s regulatory path.
Deal‑making crystallized PD‑1 anchored bispecifics as a strategic pillar:
AbbVie signed an exclusive ex‑China licensing agreement for RemeGen’s RC148 (PD‑1/VEGF bispecific) with $650 million in upfront payments and up to $4.95 billion in milestones. This explicitly positions it as a backbone for combinations–including with AbbVie’s ADC portfolio–in multiple advanced solid tumors. Together with Takeda’s partnership around IBI363, this signals that large pharma now sees bispecific backbones as critical to next‑generation IO strategy and portfolio differentiation, not just incremental line extensions.
T-cell engagers (TCEs) reached a clear clinical and commercial inflection point:
Amgen’s tarlatamab (DLL3×CD3) moved from late‑line into first‑line SCLC, with chemo‑IO combination data at ESMO 2025. It showed strong early PFS and no new safety concerns, positioning it as a likely future standard of care.
In addition, Q2 2025 sales of ~$134 million (+65% QoQ) demonstrated that T‑cell engagers can achieve meaningful uptake in solid tumors, not just hematologic malignancies.
Engineering innovation expanded the solid‑tumor addressable space for TCEs:
Janux’s JANX007 (PSMA×CD3) delivered a median rPFS of 7.5 months and a 78% 6‑month rPFS rate in heavily pre‑treated mCRPC, validating the “tumor‑activated” design and supporting movement into earlier‑line settings.
VIR Biotechnology’s dual‑masked HER2 (VIR‑5818) and PSMA (VIR‑5500) TCEs, showed meaningful tumor shrinkage/PSA responses with no grade ≥3 cytokine release syndrome (CRS) and very low high‑grade treatment-related adverse events (TRAEs). This suggests that advanced masking can overcome safety bottlenecks in solid‑tumor TCEs.
Portfolio rationalization underscored that differentiation is mandatory:
AstraZeneca’s discontinuation of Sabestomig (PD‑1×TIM‑3) after modest efficacy data, highlighted the risks of undifferentiated combinations and the need for clear efficacy or safety benefits.
Overall, bi-specifics are definitely “in the game” when it comes to solid tumors. For the most part, the assets that we thought would lead the charge are advancing as expected, and we’ll be sure to track their progression during 2026.
Prediction 2 – Synthetic lethality will come into focus
For 2025, we expected a proliferation of interest in synthetic lethality and synthetic lethal drug approaches with continued advancement in the space. In particular, we focused our attention on efforts at IDEAYA Biosciences, REPARE Therapeutics, and several other firms. Below, we offer a brief update:
- IDEAYA Biosciences’ darovasertib (IDE196) is progressing nicely, as the company shared positive phase 2 data at the 2025 ESMO conference. Other IDEAYA assets, including IDE275, IDE397, and IDE705 also remained on track. However, GSK quietly exited its synthetic lethality development partnership with IDEAYA in December, returning all of the relevant assets to IDEAYA.
- REPARE Therapeutics forged ahead with RP-3467 and RP-1664. The fourth quarter was a busy one for REPARE. In November, the company announced its entry into a definitive agreement to be acquired by Xeno Therapeutics. In December, REPARE announced the sale of RP-3467 to Gilead Sciences for up to $30 million.
- Tango Therapeutics reported positive data from its ongoing phase 1 / 2 study of vopimetastat in patients with MTAP-deleted cancers. Initial data support the potential of vopimetostat to meaningfully help patients with advanced pancreatic cancer via a once-daily pill instead of intravenous chemotherapy.
- Insilico Medicine, a company driven by generative-AI, initiated a phase 1 study for ISM3412.
- Tessellate Bio remained on track with its efforts, entering into a $570 million deal in April with Boehringer Ingelheim to develop its synthetic lethal program.
Overall, progress continued as expected. Of course, we’ll need to keep an eye on IDEAYA and their next strategic moves following the end of its partnership with GSK. In addition, we’ll monitor the situation with REPARE and Xeno Therapeutics.
Prediction 3 – Degraders will further mature as a class
2024 saw significant progress in proteolysis-targeting chimera (PROTAC) degraders. We predicted that the trend would continue—and likely accelerate—over the next 12 months. For 2025, we were anticipating an important readout of pivotal data for vepdegestrant (ARV-471), pivotal trial starts for BMS-986365 and NX-5948, and early data from a range of other assets.
Developments in this area moved forward largely as we had expected, though not without some surprises. The phase 3 trial for vepdegestrant did show “statistically significant and clinically meaningful” results. Furthermore, Pfizer and Arvinas announced that the FDA had accepted their NDA for vepdegestrant for the treatment of ESR1m, ER+/HER2- advanced breast cancer. By September, however, it was reported that Pfizer and Arvinas had decided to “wash their hands” of the therapy, as the mixed data regarding it would relegate it to 2nd line status. They decided to out-license commercialization rights for vepdegestrant to a third party. Arvinas planned to focus instead on its earlier-stage PROTAC degraders, including ARV-102, ARV-393, and ARV-806.
As expected, BMS initiated a phase 3 study for BMS-986365. The rechARge trial will evaluate it against the investigator’s choice of therapy—either a second androgen receptor pathway inhibitor (ARPI) or docetaxel—in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed after one prior ARPI. The positive clinical response in patients who were not exposed to prior chemotherapy and opioid therapy triggered the move into this earlier line of therapy.
Nurix’s NX-5948 (bexobrutideg) also remained on track. The company released positive phase 1 data in June of 2025. In October, they announced initiation of the DAYBreak pivotal single-arm Phase 2 study of NX-5948 in relapsed or refractory chronic lymphocytic leukemia (r/r CLL). The program will evaluate a 600 mg once-daily oral dose and will seek data to support a potential accelerated approval. In addition, Nurix plans a randomized confirmatory phase 3 trial to start in the first half of 2026 comparing bexobrutideg to pirtobrutinib, bendamustine + rituximab, or idelalisib + rituximab.
Other, earlier-stage assets also remained on track. These include C4 Therapeutics’ cemsidomide, Monte Rosa Therapeutics’ MRT-2359, Foghorn Therapeutics’ FHD-909, and Nurix’s NX-1607.
Prediction 4 – Cancer cachexia will attract a lot of attention
Cachexia, a complex wasting syndrome associated with cancer, is estimated to occur in up to 80% of people with advanced cancer. It cannot be fully reversed with nutritional support alone. Cachexia can reduce the efficacy of cancer treatment as well as a patient’s quality of life and the probability of survival. There is a significant unmet need regarding this condition.
In last year’s outlook, we focused our attention on Pfizer’s anti-GDF-15 antibody, ponsegromab, which was demonstrating positive phase 2 results. Those positive results continued, which Pfizer shared at the 2025 ESMO conference during October in Berlin. The one-year data update showed that benefits from earlier in the study were maintained over 12 months. Of the “117 patients with either non-small cell lung cancer, colorectal cancer, or pancreatic cancer who moved into the 12-month, open-label extension part of the trial, the average weight gain was 2.7 kg at Week 24, 4.4 kg at Week 52 and 5.2 kg at Week 64.” Late in 2025, ponsegromab entered its first pivotal trial.
Ponsegromab isn’t the only game in town, though. CatalYm is a private German biotech firm focusing on GDF-15. Its sole pipeline asset, visugromab, is being studied as a cachexia treatment and will move into a pivotal phase 2/3 trial in early 2026.
While Pfizer and CatalYm are in the lead when it comes to anti-GDF-15 projects for cancer cachexia, there are others in the mix. Currently, as least two other assets (from Aveo and GenFleet) are in phase 1 of development while five other assets from a range of companies are in the preclinical stage. Overall, there was significant activity in this space during 2025, directly in line with our expectations.
Coming Next
When all is said and done, the oncology market in 2025 turned out just as we had expected, with each of our predictions either fulfilled or well on the way to being fulfilled. While looking backwards is great for holding ourselves accountable, the real fun is looking ahead to try and figure out which way things are going. So, our next step is to stop checking the rearview mirror and focus our gaze firmly on the future.
In a few weeks, we will publish our 2026 Oncology Market Outlook. Once again, it should be an exciting year, and we can’t wait to share our thoughts about it.
In the meantime, please follow us on LinkedIn to stay up-to-date on our latest publications. In addition, please contact us via our website if you have any questions or would like to discuss development and commercial strategy for your company’s oncology product(s) or portfolio.
