Each year, the oncology development landscape becomes noisier. Late-stage assets are promoted aggressively, conference headlines amplify early signals, and investor narratives often blur the line between promise and probability. After more than 12 years leading global clinical programs across major pharmaceutical organizations, including Merck and GSK, I have learned that FDA approval in oncology is rarely about excitement, it is about evidence quality, endpoint discipline, and regulatory credibility.
For 2026, our team deliberately narrowed focus to a small group of oncology and oncology-adjacent programs with clear FDA regulatory timelines and datasets that meaningfully de-risk approval. These are not necessarily the most talked-about assets, but they are the ones where clinical logic, FDA precedent, and development strategy align.
Below, I outline seven drugs with expected FDA decisions or filings in 2026, and explain why, despite very different mechanisms and indications, each represents a possible regulatory opportunity.
1) Relacorilant + nab-paclitaxel: FDA Approval Candidate in Platinum-Resistant Ovarian Cancer (PROC)
Platinum-resistant ovarian cancer (PROC) is among the most difficult solid tumor settings in drug development, characterized by aggressive biology, limited effective therapies, and short survival once resistance emerges. In this context, incremental but statistically robust improvements in progression-free survival (PFS), particularly when accompanied by supportive overall survival (OS) trends, are considered clinically meaningful by regulators, provided toxicity does not compromise treatment delivery or quality of life. 1
Relacorilant, a selective glucocorticoid receptor modulator, was evaluated in combination with nab-paclitaxel in the Phase 3 ROSELLA trial, a randomized study designed to assess whether modulation of glucocorticoid signaling could enhance chemotherapy efficacy and overcome treatment resistance. 1 The study met its primary endpoint, demonstrating a statistically significant improvement in PFS (hazard ratio approximately 0.70), alongside an interim OS signal favoring relacorilant (median OS ~16.0 months versus ~11.5 months in the control arm), results that compare favorably with historical benchmarks in this setting. 2
From a clinical development perspective, the magnitude and consistency of the PFS benefit are particularly relevant. In PROC, FDA precedent shows that clear PFS separation with acceptable safety has supported approvals, even when OS data are immature at the time of decision, provided there is no signal of harm and the survival trend is directionally favorable. 1 Importantly, the relacorilant combination did not introduce prohibitive toxicity that would undermine its real-world feasibility, a critical consideration in heavily pretreated ovarian cancer populations. 2
In terms of regulatory, the program has progressed in a manner consistent with a viable late-line oncology filing. The FDA has accepted the NDA and assigned a PDUFA target action date of July 11, 2026, signaling that the agency considers the application sufficiently complete for substantive review. 3
Our perspective: In PROC, regulators are pragmatic. The bar is not cure, but credible delay of progression without unacceptable toxicity. Relacorilant plus nab-paclitaxel presents a dataset that is internally consistent, mechanistically plausible, and aligned with prior FDA decision-making in this indication. The combination’s ability to deliver a reproducible PFS benefit, coupled with a favorable OS trend and manageable safety profile, places it squarely within the category of late-line oncology programs that have a realistic and defensible path to approval.
2) Ga-68 edotreotide (LNTH-2501): FDA Imaging Approval for SSTR-Positive Neuroendocrine Tumors
Ga-68 edotreotide (LNTH-2501) sits in a category that is often underappreciated in oncology forecasting: diagnostic approvals that can materially shift treatment decisions without taking on the same benefit–risk burden as therapeutics. In SSTR-positive neuroendocrine tumors (NETs), SSTR-PET is not simply “better pictures”, it directly affects staging, localization of unknown primaries, selection for somatostatin-targeted therapies (including PRRT), and longitudinal monitoring, all of which have downstream clinical consequences. 4, 5
LNTH-2501 is a 2-vial kit supplied to radiopharmacies for preparation of Ga-68 edotreotide injection using generator-produced gallium, and the FDA has set a PDUFA target action date of March 29, 2026,. 6 From a regulatory perspective, this kit-based format is important because it supports standardized preparation, quality control, and reproducibility across sites, often a central focus of FDA review for radiopharmaceutical diagnostics (clinical implementation and robustness of Ga-68 SSTR. 7
From an evidence standpoint, the FDA-reviewed clinical studies supporting Ga-68 edotreotide demonstrated a positive percent agreement (PPA) of approximately 90% and a negative percent agreement (NPA) of approximately 75% versus a composite reference standard for detection of SSTR-positive lesions, a performance profile consistent with accepted regulatory benchmarks for molecular imaging agents in settings where histopathologic confirmation of every lesion is not feasible. 8
Our perspective: What matters most here is not achieving a perfect NPA, which is rarely realistic given the limitations of truth standards in whole-body imaging, but demonstrating high and reproducible PPA in the clinically relevant population, combined with operational feasibility at scale. LNTH-2501 aligns well with FDA’s established imaging approval paradigm: clearly defined indication (SSTR+ NETs), clinically meaningful use case, validated diagnostic performance metrics, and a kit-based manufacturing approach that reduces variability. When those elements are in place and manufacturing comparability is tight, imaging agents typically face a lower regulatory friction profile than novel therapeutics, making LNTH-2501 one of the higher-probability 2026 approval candidates on this list (FDA label and review framework. 6,8
3) Varegacestat (AL102): FDA Approval in Desmoid Tumors Based on Phase 3 RINGSIDE Data
Desmoid tumors are rare, locally aggressive, and clinically meaningful despite being non-metastatic, patients often face chronic pain, functional compromise, repeated procedures, and prolonged systemic therapy. In this setting, endpoints like PFS, objective response rate (ORR), and patient-relevant symptom improvement are both measurable and regulator-relevant, which is important because the FDA has already established a clear approval precedent in desmoid with nirogacestat (OGSIVEO) for adults with progressing disease requiring systemic therapy.9, 10
Varegacestat (AL102) is a next-generation gamma secretase inhibitor being developed in the Phase 3 RINGSIDE program (study listing and design. 11 The topline Phase 3 results reported that the trial met its primary endpoint of PFS, showing an 84% reduction in risk of progression or death (HR = 0.16; p<0.0001), and a confirmed ORR of 56% vs 9% with placebo (p<0.0001) by blinded independent central review. 12, 13
Our perspective: This is what “approvable” looks like in desmoid tumors: a randomized dataset with a very large and statistically unambiguous PFS effect size, coupled with a high confirmed ORR, both assessed in a way that aligns with modern FDA expectations for this disease category, as demonstrated by the agency’s prior decision on nirogacestat. 9, 10 Analytically, what stands out is not only the magnitude of benefit (HR ~0.16) but the interpretability: desmoid is measurable, progression events are clinically meaningful, and placebo-controlled PFS is a regulator-friendly endpoint. The remaining diligence questions for a consultancy-grade approval forecast are therefore concentrated in three areas: durability of benefit over time, tolerability in chronic use (since patients may remain on therapy for extended periods), and how the safety profile compares with the already-approved class precedent (nirogacestat) when regulators consider labeling and risk management. 9, 10 With the topline efficacy package already reading as “registrational,” varegacestat fits the profile of a program where the probability of approval will hinge less on whether it works and more on whether the full submission demonstrates consistent benefit-risk and a clean, regulator-ready dataset. 11, 12
4) OST-HER2: Accelerated FDA Approval Pathway in Recurrent Pulmonary Metastatic Osteosarcoma
Recurrent pulmonary metastases remain the leading cause of mortality in osteosarcoma, particularly after complete surgical resection, and there are no FDA-approved therapies specifically indicated to prevent or delay recurrence in this setting. Outcomes after metastasectomy rely largely on historical chemotherapy strategies, with reported 2-year overall survival rates often below 50%, highlighting a severe and persistent unmet need. 14, 15
OST-HER2 is an HER2-targeted immunotherapy being developed as an adjuvant strategy following complete resection of pulmonary metastases, with the goal of eradicating minimal residual disease and delaying recurrence. The biological rationale is supported by evidence that HER2 is expressed in a subset of osteosarcomas and that HER2-directed immune approaches can generate tumor-specific immune responses in this disease context. 16
In Phase 2 clinical experience reported by the company, OST-HER2 was associated with 2-year overall survival rates of approximately 75%, comparing favorably with historical controls in similar post-metastasectomy populations, supporting a potential survival advantage in a setting where randomized trials are difficult to execute. 15 Based on these data, the company has stated that it plans to pursue a BLA submission under the Accelerated Approval pathway by the end of January 2026.
Our perspective: From a regulatory standpoint, OST-HER2 fits a familiar accelerated-approval pattern in ultra-rare oncology: a life-threatening disease, no approved alternatives, biologically plausible mechanism, and a survival signal relative to well-characterized historical outcomes. The key FDA questions will center on the validity and applicability of the historical comparator, durability of benefit, and feasibility of a confirmatory strategy, rather than on novelty of mechanism. If these elements are clearly articulated, OST-HER2 represents a program with a non-trivial and defensible chance of regulatory success, despite the inherent challenges of osteosarcoma drug development.
5) Bezuclastinib: FDA Approval Outlook in Systemic Mastocytosis (Non-Advanced and Advanced)
Systemic mastocytosis is a clonal mast-cell disease most commonly driven by KIT D816V, where patients can experience substantial symptom burden (flushing, GI symptoms, anaphylaxis risk) and, depending on subtype, organ dysfunction. Objective disease markers such as serum tryptase, bone marrow mast cell burden, and KIT D816V variant allele frequency (VAF) are widely used to reflect disease activity and burden, and changes in these markers have clinical and regulatory relevance in mastocytosis programs. 17, 18
Bezuclastinib (CGT9486) is a selective KIT inhibitor evaluated in SUMMIT (NCT05186753), a randomized, double-blind, placebo-controlled Phase 2 study in non-advanced systemic mastocytosis (NonAdvSM). 19, 20 In the company’s full SUMMIT readout, bezuclastinib showed deep, quantitative improvements in objective markers at Week 24, including ≥50% reductions in serum tryptase (87.4%), bone marrow mast cell burden (75.6%), and KIT D816V VAF (80.5%), alongside clinically meaningful symptom improvement—an “activity pattern” that is difficult to achieve simultaneously in this disease. 21, 22
From a regulatory-timeline perspective, Cogent has stated that an NDA for NonAdvSM was submitted in December 2025, and that an NDA submission for advanced systemic mastocytosis (AdvSM) remains on track for 1H 2026, which positions bezuclastinib as an active 2026 regulatory story. 23
Our perspective: What makes bezuclastinib analytically compelling is the alignment of outcomes: symptom improvement plus deep reductions in disease biology (tryptase, marrow burden, KIT VAF) within a randomized, placebo-controlled framework. That combination tends to strengthen “approvability,” because it supports both patient benefit and mechanistic delivery—two pillars regulators increasingly expect in chronic, heterogeneous diseases like systemic mastocytosis. 20, 21
6) RP1 + nivolumab: FDA Accelerated Approval Review in PD-1–Refractory Melanoma
PD-1–refractory advanced melanoma remains one of the most difficult “salvage” settings in immuno-oncology, where many combinations fail to produce durable systemic control and regulators weigh response durability and interpretability very heavily. RP1 (vusolimogene oderparepvec) is an HSV-1–based oncolytic immunotherapy engineered to express GM-CSF and a fusogenic protein (GALV-GP R-) intended to enhance tumor cell killing, immunogenic cell death, and systemic anti-tumor immune activation. 24
Clinically, the strongest “signal” underpinning the program is that RP1 + nivolumab has produced meaningful systemic responses in anti–PD-1–refractory melanoma in the IGNYTE trial. 25 According to the Journal of Clinical Oncology report, the combination achieved an objective response rate of 32.9% with 15.0% complete responses, alongside a median duration of response of 33.7 months, and a safety profile described as favorable with mostly grade 1–2 adverse events. 26, 27
Regulatorily, this has not been a straight line. The FDA issued a Complete Response Letter for the original BLA in July 2025. 28 Replimune subsequently resubmitted the application, and the FDA accepted the resubmission with a PDUFA target action date of April 10, 2026. 29
Our perspective: Analytically, RP1’s approval case rests on two features that regulators prioritize in the post–PD-1 setting: (1) durability of response (a median DOR measured in years rather than months) and (2) evidence of systemic antitumor activity beyond injected lesions, not just shrinkage in injected lesions.26 The counterweight is that the program has already encountered FDA scrutiny once, meaning the 2026 review will likely focus intensely on dataset interpretability, the lack of a randomized comparator, and how convincingly the package supports generalizable benefit. If the resubmission cleanly addresses the prior CRL concerns while preserving the durability story seen in the peer-reviewed dataset, RP1 + nivolumab remains one of the more differentiated, and plausibly approvable, approaches in PD-1–refractory melanoma..28,29
