Citius Oncology Highlights Phase 1 Data in an Investigator-Initiated Study of LYMPHIR® (denileukin diftitox-cxdl) in Combination with Pembrolizumab in Recurrent or Refractory Gynecologic Malignancies
Rhea-AI Summary
Citius Oncology (Nasdaq: CTOR) reported Phase 1 data from an investigator-initiated study of LYMPHIR (denileukin diftitox-cxdl) plus pembrolizumab in recurrent or refractory gynecologic malignancies presented at ASCO 2026.
Among 21 efficacy-evaluable patients, the combination achieved a 24% overall response rate, 48% clinical benefit rate, and median progression-free survival of 20.5 months in those with clinical benefit, with manageable tolerability and no new safety signals. A Phase 2 expansion is planned.
Positive
- 24% overall response rate in 21 efficacy-evaluable patients
- 33% objective response rate in relapsed or refractory endometrial cancer after checkpoint inhibitors
- 48% of efficacy-evaluable patients achieved clinical benefit
- Median progression-free survival 20.5 months in clinical-benefit subgroup
- Duration of response up to 35 months; median 21.1 months
- No new safety signals; maximum tolerated dose not reached
Negative
- Evidence limited to 25-patient, open-label Phase 1 study
- 16 serious adverse events in seven patients at highest dose level
- One reversible Grade 3 capillary leak syndrome case at highest dose
News Market Reaction – CTOR
In the Jun 1 session, CTOR declined 0.71%, reflecting a mild negative market reaction.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Previous Clinical trial Reports
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| May 26 | ASCO data preview | Positive | +2.4% | Announced upcoming ASCO poster with 24% ORR and durable responses. |
| Mar 31 | Launch & trials update | Positive | +25.7% | Reported early LYMPHIR launch traction and positive collaboration topline data. |
| Mar 10 | Topline Phase 1 combo | Positive | -0.5% | Disclosed positive topline Phase 1 results for LYMPHIR plus pembrolizumab. |
| Mar 04 | CAR-T combo data | Positive | +2.8% | Shared preliminary LYMPHIR pre–CAR-T data in high-risk DLBCL with strong ORR. |
| Nov 11 | Early combo results | Positive | +6.3% | Reported promising preliminary Phase I pembrolizumab plus LYMPHIR results in solid tumors. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Clinical updates on LYMPHIR have generally been met with positive price reactions, though there has been at least one instance of mild divergence.
Over the last several months, CTOR has repeatedly highlighted LYMPHIR’s expanding clinical profile. Prior clinical-trial news on the pembrolizumab combinations reported a 24–27% ORR and meaningful clinical benefit rates, with presentations at major meetings such as ASTCT and ASCO. Price reactions to these clinical milestones were often positive, including moves of 25.74% and 6.3%, though one March 10, 2026 topline update saw a small -0.5% pullback. Today’s detailed Phase 1 ASCO data continue this same investigator-initiated program in recurrent or refractory gynecologic cancers.
Key Terms
progression-free survival medical
objective response rate medical
regulatory T-cells medical
immune checkpoint inhibitors medical
dose limiting toxicities medical
maximum tolerated dose medical
capillary leak syndrome medical
tumor microenvironment medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
Investigator-initiated study data presented May 30, 2026, at the American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated durable responses and manageable tolerability in heavily pre-treated patients
20.5 months of median progression-free survival observed among
Responses were observed in patients previously treated with immune checkpoint inhibitors, including a
"LYMPHIR's ability to transiently deplete immunosuppressive regulatory T-cells may help address immune resistance in the tumor microenvironment and enhance the effect of checkpoint inhibitors. The encouraging clinical signals and tolerability profile observed in this study support continued clinical evaluation of this "chemo-free" immunomodulatory approach, especially in tumors where resistance to checkpoint inhibitors remains a significant challenge," said Dr. Myron S. Czuczman, Chief Medical Officer of Citius Oncology.
The open-label Phase 1 study evaluated LYMPHIR in combination with pembrolizumab in 25 heavily pre-treated patients (21 evaluable for efficacy) with recurrent or metastatic solid tumors, primarily gynecologic malignancies. Enrolled patients had received a median of five prior therapies, and more than half had previously received anti-PD-1 or PD-L1 therapy.
Key Efficacy and Safety findings presented at ASCO included:
24% Overall Response Rate (ORR) among the 21 efficacy-evaluable patients (5 partial responses).- Median duration of response (mDOR) had not yet been reached because only 1 of the 5 partial responders had progressed at the time of analysis (
80% of PRs were continuing to experience clinical benefit). The current duration of response times (time since PR was achieved) were 4.2-35 months with a median of 21.1 months. 33% ORR in endometrial cancer patients previously treated with checkpoint inhibitors, including one patient with an ongoing response greater than three years.48% of efficacy-evaluable patients (10 of 21) achieved clinical benefit, defined as complete response (CR), partial response (PR), or durable stable disease lasting at least six months:- Median progression-free survival (mPFS) of 20.5 months (
95% CI: 6.5 – NA) among the 10 patients who achieved clinical benefit; overall mPFS across all 21 efficacy-evaluable patients was 5.8 months (95% CI: 2.2 – NA); - 5 patients had a PFS of > 20 months including 1 patient with > 30 months PFS;
- Median progression-free survival (mPFS) of 20.5 months (
- Of the 24/25 pts evaluable for dose limiting toxicities (DLTs), only 1 case of reversible Gr 3 capillary leak syndrome (CLS) was observed at the highest dose level. A maximum tolerated dose was not achieved.
- 16 serious adverse events were observed in seven patients treated at the highest dose level. No new safety signals or grade 3 or greater immune-related adverse events were observed.
Dr. Alexander Olawaiye, a professor and one of the gynecologic cancer researchers at UPMC Magee-Womens Hospital and lead investigator of the study, added, "Patients with recurrent gynecologic malignancies who progress following immunotherapy often have limited treatment options. The clinical activity observed with denileukin diftitox-cxdl plus pembrolizumab, including durable responses and prolonged disease control in heavily pre-treated patients, is notable. Given the lack of effective salvage treatments for these patients, especially those that have failed prior immune-checkpoint inhibition, the novel combination of LYMPHIR plus pembrolizumab provides a potential viable therapeutic option. Importantly, the safety profile observed was manageable in this heavily pre-treated population, supporting continued evaluation in larger studies."
Ongoing translational studies are evaluating the impact of the combination on regulatory T-cells, immune effector cells, and the tumor microenvironment to help identify potential biomarkers in order to optimize future development strategies. A Phase 2 expansion study is being planned to further evaluate the combination in gynecologic cancers, including less heavily pre-treated and prior immunotherapy-exposed patient populations.
About the Study
This open‑label, dose‑escalation, investigator‑initiated Phase 1 study (NCT05200559), led by Dr. Alexander B Olawaiye at UPMC Magee‑Womens Hospital, enrolled 25 patients with recurrent or metastatic solid tumors who had received at least one prior line of therapy. LYMPHIR was administered intravenously on Days 1–3 of each 21‑day cycle at escalating doses (3, 6, 9, and 12 mcg/kg), along with pembrolizumab (200 mg IV) on Day 1. Patients who completed eight cycles of combination therapy were continued on pembrolizumab monotherapy until disease progression. Citius Oncology provided study drug and financial support to the investigator-initiated study; the study was designed, conducted, and analyzed by the UPMC investigators.
Important note on investigational use: The use of LYMPHIR in this study was investigational and outside of its FDA-approved indication of relapsed or refractory Stage I–III cutaneous T-cell lymphoma. LYMPHIR is not approved by the FDA for the treatment of gynecologic malignancies or any solid tumor, and the safety and efficacy of LYMPHIR in this setting have not been established. This Phase 1 study was not designed or powered to evaluate clinical efficacy, and no conclusions can be drawn regarding comparative effectiveness or long-term outcomes. Early-stage clinical data may not be predictive of results from larger or later-stage studies.
About Gynecologic Cancers
Recurrent or metastatic ovarian and endometrial cancers are two of the most common gynecologic malignancies in
About LYMPHIR (denileukin diftitox‑cxdl)
LYMPHIR is a targeted immune therapy for relapsed or refractory cutaneous T-cell lymphoma (CTCL) indicated for use in Stage I-III disease after at least one prior systemic therapy. It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin (DT) fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl-associated anti-tumor activity is achieved via a direct cytocidal action on IL-2R-expressing tumors and depletion of host immunosuppressive regulatory T lymphocytes (Tregs).
In 2021, reformulated denileukin diftitox received regulatory approval in
About Citius Oncology, Inc.
Citius Oncology, Inc. (Nasdaq: CTOR) is a platform to develop and commercialize novel targeted oncology therapies. In December 2025, Citius Oncology launched LYMPHIR, approved by the FDA for the treatment of adults with relapsed or refractory Stage I–III CTCL who had had at least one prior systemic therapy. Management estimates the initial CTCL market for LYMPHIR currently exceeds
Forward-Looking Statements
This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius Oncology. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "plan," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are: our need for substantial additional funds and our ability to raise additional money to fund our operations for at least the next 12 months as a going concern; our ability to successfully commercialize LYMPHIR and establish a sustainable revenue stream; our ability to regain compliance with Nasdaq's continued listing standards; our ability to obtain, perform under and maintain third party agreements and relationships, including obtaining a new bulk drug substance supplier; risks relating to the results of research and development activities, including those from our existing and any new pipeline assets; early-stage clinical data may not be predictive of results from larger or later-stage studies; our ability to secure and maintain strategic partnerships and expand international access to LYMPHIR; the estimated markets for LYMPHIR and our product candidates and the acceptance thereof by any market; our ability to use the latest technology to support our commercialization efforts for LYMPHIR; physician and patient acceptance of LYMPHIR in a competitive treatment landscape; our reliance on third-party logistics providers, distributors, and specialty pharmacies to support commercial operations; our ability to educate providers and payers, secure adequate reimbursement, and maintain uninterrupted product supply; post-marketing requirements and ongoing regulatory compliance related to LYMPHIR; the ability of LYMPHIR and our product candidates to impact the quality of life of our target patient populations; our ability to procure cGMP commercial-scale supply; risks related to our growth strategy; patent and intellectual property matters; government regulation; as well as other risks described in our Securities and Exchange Commission ("SEC") filings. These risks have been and may be further impacted by any future public health risks. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our SEC filings which are available on the SEC's website at www.sec.gov, including in Citius Oncology's Annual Report on Form 10-K for the year ended September 30, 2025, filed with the SEC on December 23, 2025. These forward-looking statements speak only as of the date hereof, and we expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.
REFERENCES:
- American Cancer Society. Cancer Facts & Figures 2026 (projected). Atlanta: American Cancer Society; 2026. https://www.cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html
- National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER). Cancer Stat Facts: Uterine and Ovarian Cancer. https://seer.cancer.gov/statfacts/html/ovary.html
LYMPHIR (denileukin diftitox‑cxdl)
INDICATION
LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with r/r Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: CAPILLARY LEAK SYNDROME
Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity.
WARNINGS AND PRECAUTIONS
Capillary Leak Syndrome
LYMPHIR can cause capillary leak syndrome (CLS), including life-threatening or fatal reactions. CLS was defined in the clinical trials as the occurrence of at least 2 of the following symptoms at any time during LYMPHIR therapy: hypotension, edema, and serum albumin <3 g/dL. These symptoms were not required to occur simultaneously to be characterized as capillary leak syndrome.
As defined, CLS occurred in
Regularly assess patients for weight gain, new onset or worsening of edema, dyspnea, and hypotension (including orthostatic changes). Monitor serum albumin levels prior to the initiation of each cycle of therapy and more often as clinically indicated.
Withhold, reduce dose, or permanently discontinue based on severity. If LYMPHIR is withheld, resume LYMPHIR following resolution of CLS and when serum albumin is greater than or equal to 3 g/dL.
Visual Impairment
LYMPHIR can cause serious visual impairment, including changes in visual acuity and color vision. In the pooled population across 3 clinical trials, visual impairment occurred in
Perform baseline ophthalmic examination and monitor as clinically indicated. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, or blurred vision, refer for ophthalmologic evaluation.
Withhold LYMPHIR until visual impairment resolves or permanently discontinue based on severity.
Infusion-Related Reactions
LYMPHIR can cause serious infusion-related reactions. Infusion-related reactions were reported in
Premedicate patients for the first three cycles prior to starting a LYMPHIR infusion. Monitor patients frequently during infusion. For Grade 2 or higher infusion reactions, premedicate at least 30 minutes prior to each subsequent infusion with a systemic steroid for at least 3 cycles.
Interrupt or discontinue LYMPHIR based on severity. Institute appropriate medical management.
Hepatotoxicity
LYMPHIR can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold, reduce dose, or permanently discontinue LYMPHIR based on severity.
Embryo-Fetal Toxicity
Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of LYMPHIR. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 days following the last dose of LYMPHIR.
ADVERSE REACTIONS
The most common adverse reactions (≥
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. There are no available data on the use of LYMPHIR in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with denileukin diftitox.
Denileukin diftitox-cxdl causes depletion of regulatory T lymphocytes (Treg), immune activation, and capillary leak syndrome, compromising pregnancy maintenance. Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2
Lactation
Risk Summary
No data are available regarding the presence of denileukin diftitox-cxdl in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LYMPHIR and for 7 days after the last dose.
Females and Males of Reproductive Potential
Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman.
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating LYMPHIR.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with LYMPHIR and for 7 days after the last dose.
Infertility
Males
Based on findings in rats, male fertility may be compromised by treatment with LYMPHIR. The reversibility of the effect on fertility is unknown.
Pediatric Use
Safety and effectiveness of LYMPHIR in pediatric patients have not been established.
Geriatric Use
Of the 69 patients with Stage I-III r/r CTCL who received LYMPHIR, 34 patients (
You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Citius Oncology at 1-844-459-6744.
Please read Important Safety Information and full Prescribing Information, including Boxed WARNING, for LYMPHIR.
Investor Contact:
Ilanit Allen
ir@citiuspharma.com
908-967-6677 x113
Media Contact:
STiR-communications
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SOURCE Citius Oncology, Inc.