What drugs are in development for Ovarian Cancer?

Overview of Ovarian Cancer
Ovarian cancer remains one of the most lethal gynecologic malignancies in women worldwide. It is characterized by its late diagnosis, aggressive behavior and clinical heterogeneity, and despite some advances in treatment over the past decades, its overall survival remains suboptimal. An in‐depth understanding of the disease is essential for developing more effective therapies. Research from synapse has consistently reported that about 90% of ovarian cancers are of epithelial origin with further subtyping (e.g., high‐grade serous, clear cell, endometrioid, and mucinous) that greatly influences prognosis and management. In addition, ovarian cancer can also include borderline tumors and primary peritoneal or fallopian tube cancers, which may share some molecular features with classic ovarian carcinomas. This heterogeneity—both at the molecular and clinical levels—requires that drug development strategies address multiple disease pathways and resistance mechanisms.

Types and Stages
Ovarian cancer is composed primarily of epithelial tumors, which account for more than 90% of diagnoses, while a smaller proportion includes germ cell and sex cord–stromal subtypes. The most common and aggressive subtype is high‐grade serous ovarian cancer; it is typically diagnosed at advanced International Federation of Gynecology and Obstetrics (FIGO) stages III or IV, when the tumor has spread beyond the ovaries. The histological diversity is complemented by differences in molecular pathogenesis; for instance, high‐grade serous carcinomas are notoriously associated with TP53 mutations and homologous recombination deficiency, including BRCA mutations, while other forms such as clear cell or endometrioid cancers each have distinctive molecular signatures that may influence therapeutic responses. This diversity makes it important to consider both the pathological grade and the molecular drivers when designing targeted therapies.

Current Treatment Options
Standard therapeutic approaches for ovarian cancer have long centered on maximal cytoreductive surgery followed by combination chemotherapy—primarily platinum-based agents in combination with taxanes. In advanced stages, patients may also receive intraperitoneal chemotherapy or maintenance therapies including poly (ADP-ribose) polymerase inhibitors (PARPi) for those who harbor BRCA mutations or homologous recombination defects. Additionally, antiangiogenic agents such as bevacizumab have been integrated into treatment regimens to delay progression. Although these modalities have improved progression-free survival (PFS), overall survival (OS) remains limited due to challenges including chemoresistance and disease recurrence. This context underscores the need for new drugs with novel mechanisms that can overcome these challenges and improve outcomes.

Drug Development Pipeline for Ovarian Cancer
The drug development pipeline for ovarian cancer includes a broad spectrum of approaches ranging from early-stage preclinical research to advanced clinical trials. Increasingly, emphasis is placed on targeting key molecular pathways and immune evasion mechanisms that drive tumour progression and resistance. The pipeline is highly dynamic and multifaceted, combining novel small molecules, biologic agents, and innovative combination therapies.

Preclinical Research
In the preclinical arena, researchers are exploring numerous promising agents that target pathways implicated in ovarian tumour biology. Preclinical studies have focused on several fronts:

• Targeting the DNA damage response: Given the central role of homologous recombination deficiency in high-grade serous ovarian cancer, next-generation PARP inhibitors are being developed to enhance efficacy and overcome resistance. Preclinical models are evaluating modifications in drug structure to enhance the penetration of ovarian tumour cells and reduce toxicity, with early data showing improved outcomes when these agents are combined with other targeted drugs.

• Novel targeted small molecules: Multiple agents are under preclinical evaluation targeting kinases and cell cycle regulators. For instance, inhibitors of WEE1 kinase, ATR kinase, and PI3K/AKT/mTOR pathway inhibitors are being tested because these pathways have emerged as essential for tumour cell survival in chemoresistant ovarian cancer models. These agents are being designed to interrupt tumour proliferation and to potentiate the effects of conventional chemotherapy. Preclinical research indicates that these molecules can reduce cell viability in resistant ovarian cancer cell lines and in xenograft models.

• Antibody–drug conjugates (ADCs) and targeted immunoconjugates: Antibody-based therapeutics directed at cell surface antigens specific to ovarian cancer cells, such as folate receptor α and CA125 (MUC16), are in vigorous preclinical development. ADCs combine the specificity of monoclonal antibodies with potent cytotoxic payloads and have demonstrated promising tumour killing in preclinical models, particularly against cells expressing high levels of these target antigens. In addition, emerging targets like the CT45 antigen have led to the development of immunotherapies that are currently being tested in preclinical settings. Patents and early reports from synapse describe methods for targeting CT45 with immunotherapeutic agents to overcome immune escape in ovarian cancer.

• Innovative drug delivery systems: Preclinical research is also focused on improving delivery through novel drug carriers such as nanoparticles, hydrogels, and supramolecular carriers to enhance drug bioavailability and reduce systemic toxicity. These advanced formulations aim to overcome the physical barriers inherent to ovarian tumours, such as the dense extracellular matrix and aberrant vasculature. Studies have shown that nanocarrier systems can improve the therapeutic index of traditional chemotherapeutic drugs as well as new targeted agents.

Collectively, the preclinical research phase is robust, with significant efforts to identify drug candidates that modulate multiple pathways relevant to tumour cell survival and metastasis in ovarian cancer. Early data from these studies provide strong rationale for advancing several candidates into clinical trials.

Clinical Trials Phases
The transition from preclinical research to human trials marks a critical step in drug development. Currently, numerous agents and combinations are in various phases of clinical testing:

• Phase I trials are primarily focused on determining safety, tolerability, and pharmacokinetics of new agents in a small cohort of patients. Drugs in development such as novel PARP inhibitors with modified structures, cell cycle checkpoint inhibitors (e.g., WEE1 inhibitors), and early immunotherapeutic candidates like bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies for ovarian cancer are being evaluated in this phase. Early signals from these trials provide important dose‐limiting toxicity (DLT) and maximum tolerated dose (MTD) data for future studies.

• Phase II trials investigate preliminary efficacy alongside safety in a larger cohort. Recent examples include trials evaluating combination strategies such as PARP inhibitors with antiangiogenic agents (e.g., cediranib with olaparib) which have shown promising improvements in progression-free survival. Other Phase II studies target new molecular entities including next-generation kinase inhibitors and novel monoclonal antibodies directed at ovarian cancer–specific antigens. In addition, early-phase trials for immunotherapeutic agents such as checkpoint inhibitors are also ongoing; these trials often evaluate biomarkers like PD-L1 expression or microsatellite instability (MSI) to stratify patients and assess response rates.

• Phase III trials are designed to conclusively demonstrate the efficacy of a new agent or combination therapy compared to standard of care. Several agents already approved for maintenance therapy in ovarian cancer, such as olaparib, niraparib, and rucaparib, continue to be investigated in expanded Phase III settings, sometimes in combination with other agents like bevacizumab, to further extend clinical benefits. Simultaneously, novel drug candidates such as targeted antibody–drug conjugates and selective kinase inhibitors are beginning to be evaluated in these larger trials. Adaptive trial designs and basket trials have increasingly been adopted to accelerate the evaluation process by allowing simultaneous testing across multiple subtypes of ovarian cancer and incorporating biomarker stratification to optimize patient selection.

The clinical trials pipeline is a dynamic landscape aimed at refining existing therapies through combination regimens and by introducing new agents that exploit emerging biological insights. This pipeline benefits from improved trial designs that incorporate adaptive methods and real‐world evidence, ultimately facilitating faster regulatory review and better therapeutic outcomes.

Innovative Therapies and Approaches
New agents in development for ovarian cancer are not limited to modifications of traditional chemotherapy but also feature innovative approaches that aim to overcome resistance mechanisms and harness the immune system. These innovative therapies fall broadly into two categories: targeted therapies and immunotherapies.

Targeted Therapies
Targeted therapeutic agents are designed to interact specifically with molecular pathways or antigens that are overexpressed or mutated in ovarian cancer cells. Several promising avenues are being pursued:

• PARP Inhibitors and Beyond
PARP inhibitors (PARPi) represent one of the most significant breakthroughs in ovarian cancer therapy. While drugs such as olaparib, niraparib, and rucaparib have already garnered FDA approval for maintenance therapy, new generations of PARPi are in development to improve specificity, reduce side effects, and overcome resistance mechanisms. Researchers are exploring combinations of PARPi with other agents such as kinase inhibitors and antiangiogenics to potentiate their antitumour effects. These combinations are based on the rationale that simultaneous targeting of DNA repair and cell survival pathways will have a synergistic effect against tumour cells harboring homologous recombination defects.

• Kinase Inhibitors and Cell Cycle Checkpoint Blockers
A number of small molecule inhibitors targeting critical kinases involved in cell cycle regulation and DNA damage response are under development. WEE1 inhibitors are one notable class that disrupt the cell cycle checkpoint, forcing tumour cells with unrepaired DNA damage into mitotic catastrophe. In preclinical models, these agents have shown substantial activity in ovarian cancer cells, especially in combination with chemotherapy. Similarly, ATR inhibitors and PI3K/AKT/mTOR pathway inhibitors are being tested for their ability to block survival signals in chemoresistant tumours. In addition, some agents targeting growth factor receptors—such as inhibitors of VEGF receptor signaling—are in Phase II and III trials, often in combination with other targeted therapies.

• Antibody–Drug Conjugates (ADCs) and Monoclonal Antibodies
Antibody–drug conjugates represent a unique class of targeted therapies that combine the specificity of monoclonal antibodies with the potent cytotoxicity of traditional chemotherapeutic agents. ADCs targeting folate receptor α and CA125 (MUC16), which are highly expressed on many ovarian cancer cells, are currently in development. Recent preclinical and early clinical evidence suggests that these ADCs can selectively deliver cytotoxic payloads, thereby minimizing systemic toxicity while maximizing tumour cell kill. In addition, novel targets such as CT45 are being explored for immunoconjugate formats, a strategy supported by recent patents.

• Novel Small Molecule Inhibitors
Beyond PARPi and kinase inhibitors, other novel small molecules are being studied in the context of ovarian cancer. These compounds target various pathways including those related to angiogenesis (e.g., cediranib, anlotinib) and the tumour microenvironment, as well as inhibitors of epigenetic modifiers and non-coding RNA regulators, which have emerged as potential drivers of chemoresistance. These agents are often evaluated in combination with standard chemotherapeutics or with other targeted therapies in hopes of achieving synergistic effects.

Together, these targeted therapies embody a move toward precision oncology, where treatments are tailored to the molecular profile of an individual’s tumour. This approach is expected to enhance efficacy and mitigate adverse effects, with ongoing research aimed at identifying the most effective drug combinations for distinct ovarian cancer subtypes.

Immunotherapies
Immunotherapy has revolutionized the treatment landscape of various cancers, and its potential in ovarian cancer is under active investigation. Immunotherapeutic approaches aim to stimulate the patient’s own immune system to recognize and attack cancer cells, thereby overcoming immune evasion mechanisms that are common in ovarian tumours.

• Checkpoint Inhibitors
Checkpoint blockade agents, including PD-1/PD-L1 inhibitors such as pembrolizumab and dostarlimab, have shown promise in several tumour types and are now being tested in ovarian cancer trials. Although patient selection based on biomarkers such as microsatellite instability (MSI) and PD-L1 expression is critical, preliminary evidence suggests that a subset of ovarian cancer patients may benefit significantly from checkpoint inhibition. These therapies are especially attractive when used in combination with agents that increase tumour immunogenicity, such as PARP inhibitors or antiangiogenic drugs, which may convert “cold” tumours into “hot” ones that are more susceptible to immune-mediated attack.

• Cancer Vaccines and Adoptive Cell Therapies
Therapeutic cancer vaccines are designed to elicit or augment an immune response against tumour-specific antigens. Several vaccine candidates targeting antigens like NY-ESO-1, MUC16, and folate receptor α are in early-phase clinical trials, with some studies showing encouraging immunological responses in ovarian cancer patients. In parallel, adoptive cell therapies—including the use of chimeric antigen receptor (CAR) T cells and tumour infiltrating lymphocytes (TILs)—are also being developed. These therapies involve the ex vivo expansion and genetic modification of a patient’s own immune cells to enhance their ability to target ovarian cancer cells. Early results from Phase I studies indicate that these strategies can induce durable responses in some heavily pretreated patients, though challenges in persistence and safety remain to be addressed.

• Combination Immunotherapy Approaches
Given the complexity of the ovarian tumour microenvironment (TME), combination immunotherapeutic strategies are emerging as a promising direction. Clinical trials are now investigating the synergistic effects of combining checkpoint inhibitors with PARPi, antiangiogenic agents, and even novel immunomodulatory compounds. For example, combination regimens that integrate PD-1 blockade with angiogenesis inhibitors have demonstrated potential in early-phase trials by simultaneously targeting immune evasion and tumour vascular support. Such combination strategies aim to address both tumour intrinsic factors and the supportive TME that contribute to immune suppression.

In summary, immunotherapies for ovarian cancer represent a rapidly evolving field that seeks to exploit the unique immunological characteristics of the disease. Although not all patients respond to current immune therapies, ongoing research is focused on identifying predictive biomarkers and optimizing combination strategies to enhance efficacy while minimizing toxicities.

Challenges and Future Directions
Despite significant progress in the development of new drugs for ovarian cancer, several challenges continue to hamper clinical success. Overcoming these barriers is critical to realizing the full potential of both targeted therapies and immunotherapies in improving patient outcomes.

Current Challenges in Drug Development
One of the foremost challenges in drug development for ovarian cancer is the inherent heterogeneity of the disease. The wide variety of histological and molecular subtypes complicates clinical trial design and patient selection. Drug resistance, whether intrinsic or acquired, remains a pervasive obstacle; many patients initially respond to treatment only to develop chemoresistance leading to recurrence. For example, platinum resistance and adaptive mechanisms that restore DNA repair capabilities in the face of PARP inhibition are well documented, with studies showing that up to 46% of recurrent high-grade serous ovarian cancers develop resistance through mechanisms such as restoration of homologous recombination.

Another key challenge is the tumor microenvironment, which fosters immune evasion and impedes effective drug delivery. Ovarian tumours often exhibit dense stromal components and an immunosuppressive milieu that limit the efficacy of both traditional chemotherapies and novel immunotherapies. In addition, the blood–tumour barrier and poor vascular normalization hinder drug penetration. Efforts to develop nanoparticle-based delivery systems and other advanced formulations are ongoing to address these issues.

Furthermore, many novel drugs face challenges in early clinical trials due to limited sample sizes and the difficulty of demonstrating clear benefit over existing standards of care. Adaptive and basket trial designs are being developed to accelerate drug approval and reduce costs, but these innovative trial formats require complex statistical models and regulatory collaboration. The high attrition rates in oncology drug development—where only a fraction of promising preclinical candidates achieve FDA approval after years of clinical testing—underscore the immense challenge of bringing new drugs to market.

Future Research and Development Trends
Looking ahead, several promising trends are emerging in the field of ovarian cancer drug development. First, the integration of precision medicine through biomarker-driven approaches is expected to play a critical role in tailoring therapies to individual patients. Advances in genomics, proteomics, and other “‑omic” technologies are enabling researchers to identify novel drug targets and predictive biomarkers that can more accurately stratify patients for appropriate therapies. For instance, biomarkers such as homologous recombination deficiency (HRD), tumor mutation burden (TMB), and PD-L1 expression are being used not only to select patients for PARPi or checkpoint inhibitor therapies but also to guide combination treatment strategies.

Second, the development of combination therapies appears likely to be the way forward given the multifactorial nature of ovarian carcinogenesis. Combinations of targeted therapies (e.g., PARPi with antiangiogenic agents or kinase inhibitors) appear promising in overcoming resistance and improving survival outcomes. Furthermore, combinations of immunotherapies with standard agents or with other novel combinations are also expected to become a cornerstone of future treatments. These combinations benefit from the synergistic targeting of both tumour cell intrinsic vulnerabilities and the immunosuppressive tumour microenvironment.

Third, innovative clinical trial designs such as adaptive Phase II/III and basket trials are being increasingly adopted. These designs allow simultaneous evaluation of several agents or treatment combinations across multiple ovarian cancer subtypes and incorporate interim analyses to facilitate earlier decision-making regarding efficacy. Such trial designs not only speed up the clinical development process but also reduce the overall exposure of patients to potentially ineffective treatments.

There is also a push toward developing therapies that tackle cancer stem cells as a means to reduce recurrence and metastasis. Research focused on cancer stem cell biology has led to the identification of novel targets that may be exploited to prevent tumour regrowth after initial treatment. In parallel, there is a movement toward developing advanced drug delivery platforms—such as nanoparticles, hydrogels, and supramolecular systems—that can improve the biodistribution of drugs and reduce systemic toxicity.

Finally, regulatory agencies are becoming more amenable to expedited pathways for drugs that address unmet medical needs in ovarian cancer. Initiatives such as Project FrontRunner have spurred the development of surrogate endpoints to potentially shorten the time to approval. These initiatives are expected to encourage pharmaceutical companies to accelerate the development of innovative therapeutic combinations that might otherwise be stalled by conventional regulatory hurdles.

Conclusion
In conclusion, the landscape of drugs in development for ovarian cancer is complex, diverse and rapidly evolving. The overall approach to drug development can be visualized in a hierarchical and general-specific-general structure. Broadly speaking, ovarian cancer is a highly heterogeneous disease primarily affecting epithelial tissues, with subtypes such as high‐grade serous, clear cell, endometrioid, and mucinous cancers creating challenges for uniform treatment. Standard treatments have traditionally comprised surgery and platinum/taxane-based chemotherapy, with recent additions of PARP inhibitors and antiangiogenic agents providing incremental improvements. However, owing to high recurrence rates and the development of chemoresistance, novel drugs are urgently needed.

The drug development pipeline encompasses extensive preclinical research, where new compounds targeting DNA damage response, cell cycle regulation, specific tumour antigens, and improved delivery systems are being identified and refined. These efforts are complemented by clinical trials using innovative designs—from early-phase safety and dosing studies to adaptive, biomarker-driven Phase II/III trials—to test and validate promising agents. Among the innovative therapies under development, targeted agents (such as next-generation PARP inhibitors, kinase inhibitors, ADCs, and agents targeting novel antigens like CT45) and immunotherapies (including checkpoint inhibitors, cancer vaccines, and adoptive cell therapies) are showing great promise in early studies. These approaches are designed to overcome the intrinsic and acquired resistance mechanisms in ovarian cancer while also harnessing the immune system to achieve durable responses.

Despite these advances, major challenges remain. Ovarian cancer’s inherent heterogeneity, complex tumour microenvironment, and high rates of drug resistance require multidimensional strategies and well-designed combination therapies. The need for predictive biomarkers and improved drug delivery systems is pressing, and emerging trial designs such as basket trials and adaptive Phase II/III protocols are pivotal to accelerating progress in this field. Collaborative efforts among regulatory agencies, academic researchers, and pharmaceutical companies – supported by data from reliable sources such as synapse – will be essential to move these innovative therapies from bench to bedside.

Thus, the future of ovarian cancer drug development lies in a continuous, iterative effort to refine targeted agents, develop novel immunotherapeutic strategies, and implement advanced clinical trial designs. By addressing the current challenges and building on the promising trends in preclinical and clinical research, there is significant hope that new drugs currently in development will not only extend survival but also improve the quality of life for ovarian cancer patients. Continued commitment to translational research and precision medicine is paramount for transforming the current therapeutic landscape and ultimately eradicating this deadly disease.