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New Two-year Follow-up of Genentech’s Columvi Extends Overall Survival in Relapsed or Refractory Diffuse Large B-cell Lymphoma Patients

On May 22, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported two-year follow-up data from the Phase III STARGLO study. After a median follow-up of 24.7 months, data showed a 40% improvement in overall survival (OS) for patients treated with Columvi (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) and median OS was not reached, compared to 13.5 months for Rituxan (rituximab) plus GemOx (R-GemOx) (Press release, Genentech, MAY 22, 2025, View Source [SID1234653350]). These updated data continue to demonstrate the statistically significant and clinically meaningful survival benefit of this off-the-shelf, fixed-duration Columvi combination for people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant (ASCT). Data will be presented in an oral session at the 61st American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), May 30 – June 3, 2025.

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"We are encouraged that the two-year follow-up data for Columvi reinforces its potential to extend the lives of many patients where prognosis has historically been poor," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "These findings demonstrate the potential lasting benefits of early and effective treatment initiation with a bispecific antibody for people with relapsed or refractory disease."

"When cancer comes back or doesn’t respond to treatment, it’s devastating for patients with DLBCL given the aggressive nature of the disease," said Haifaa Abdulhaq, M.D., professor, University of California San Francisco (UCSF), director of Hematology, UCSF Fresno. "In my community practice, I’ve seen the potential of this Columvi combination to help patients start treatment quickly – providing lasting remissions and more time without ongoing therapy."

The benefit across key secondary endpoints, including progression-free survival (PFS) and complete remission (CR), was maintained for patients treated with the Columvi combination. There was a 59% reduction in the risk of disease progression or death (hazard ratio =0.41, 95% confidence interval: 0.29–0.58) and more than twice as many patients sustained a CR (58.5% vs. 25.3%). Among patients with a CR at the end of the treatment period, 89% were alive and 82% had maintained remission one year after treatment. Safety of the combination remained unchanged from the previous analysis and was consistent with the known safety profiles of the individual medicines. Patients received a higher median number of cycles of the Columvi combination (11 versus 4), due to disease progression in the R-GemOx arm. A higher rate of adverse events (AEs) was observed with the Columvi regimen. One of the most common AEs was cytokine release syndrome, which was generally low grade.

Given the wide adoption of global treatment guidelines in real-world clinical practice, there are no biological or clinical differences in DLBCL management worldwide. While second-line therapies have advanced, DLBCL can progress rapidly and many people are not candidates for, cannot tolerate, or do not have access to latest therapies. There is an urgent need for treatments that are rapidly available upon a diagnosis of relapse, that can manage the disease and improve long-term outcomes.

Based on the STARGLO data, this Columvi combination is approved in more than 30 countries for people with R/R DLBCL who are not candidates for ASCT, including countries throughout the EU. Columvi in combination with GemOx was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) as an NCCN category 1 preferred recommendation for the treatment of people with second-line DLBCL who are not intended to proceed to transplant.† Columvi monotherapy has been approved for use in R/R DLBCL after two or more prior lines of therapy in more than 60 countries worldwide.

Columvi is part of Genentech’s industry-leading CD20xCD3 bispecific antibody program. Together with the clinical development of off-the-shelf allogeneic CAR T-therapies, Genentech aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems.

†NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

About the STARGLO study

The STARGLO study [GO41944; NCT04408638] is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Columvi (glofitamab-gxbm) in combination with gemcitabine plus oxaliplatin (GemOx) versus Rituxan (rituximab) in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and who are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Preclinical research indicated an increased antitumor effect when combining Columvi with GemOx over GemOx alone, so the STARGLO study was initiated to further explore the potential complementary effects of the treatment combination. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability.

About Columvi (glofitamab-gxbm)

Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Columvi is part of Genentech’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development program, which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Genentech is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma.

As part of Genentech’s efforts to elevate treatment standards in the earlier stages of DLBCL, where there is the best opportunity to improve long-term outcomes and prevent relapse, Columvi is also being investigated in combination with other medicines in previously untreated DLBCL in the Phase III SKYGLO study [GO44145; NCT06047080].

About Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma in the U.S. Approximately 160,000 people worldwide are diagnosed with DLBCL each year, with comparable incidence rates across regions. Medical practices, including pathological classification, diagnosis, staging, initial treatment and relapse management, are similarly approached worldwide. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Improving treatments earlier in the course of the disease and providing much-needed alternative options could help to improve long-term outcomes.

Columvi U.S. Indication

Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer.

It is not known if Columvi is safe and effective in children.

The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about Columvi?

Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death.

Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including:

fever of 100.4°F (38°C) or higher
chills or shaking
fast or irregular heartbeat
dizziness or light-headedness
trouble breathing
shortness of breath
Due to the risk of CRS, you will receive Columvi on a "step-up dosing schedule".

A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1).
You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller "step-up" doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose.
You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2).
If your dose of Columvi is delayed for any reason, you may need to repeat the "step-up dosing schedule".
If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi.
Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions.
Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects.

Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away.

What are the possible side effects of Columvi?

Columvi may cause serious side effects, including:

Cytokine Release Syndrome.
Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:
headache
confusion and disorientation
difficulty paying attention or understanding things
trouble speaking
sleepiness
memory problems
numbness, tingling, or weakness of the hands or feet
dizziness
shaking (tremors)
Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat.
Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare:
tender or swollen lymph nodes
pain or swelling at the site of the tumor
chest pain
cough
trouble breathing
The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness.

The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).

Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects.

Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you:

have an infection
have kidney problems
are pregnant or plan to become pregnant. Columvi may harm your unborn baby
Females who are able to become pregnant:

Your healthcare provider should do a pregnancy test before you start treatment with Columvi.
You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi.
are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving Columvi?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.

These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi.

You may report side effects to the FDA at (800) FDA-1088 or View Source You may also report side effects to Genentech at (888) 835-2555.

Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit View Source

Innate Pharma Highlights Durable Responses to Lacutamab in Sezary Syndrome and Mycosis Fungoides

On May 22, 2025 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported the presentation of long-term follow-up data from the Phase 2 TELLOMAK clinical trial evaluating lacutamab, an anti-KIR3DL2 monoclonal antibody, in patients with Sézary syndrome (SS) and mycosis fungoides (MF), two rare and aggressive forms of cutaneous T-cell lymphoma (CTCL) (Press release, Innate Pharma, MAY 22, 2025, View Source [SID1234653349]). The results will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting, in Chicago, Illinois.

Lacutamab was recently granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of Sézary syndrome, underscoring its potential to address critical needs in advanced CTCL.

As of October 17, 2024, data cut-off, lacutamab demonstrated compelling and sustained clinical activity in heavily pretreated patients, with a global ORR of 42.9% for SS and 19.6% for MF. With longer follow-up, we observed improved median duration of response of 25.6 months in SS and 13.8 months in MF, highlighting the durability of responses in these challenging indications1.

In addition, lacutamab was very well tolerated supporting the strong rationale for further investigations in combination beyond CTCL, especially in combination with other anti-lymphoma agents in peripheral T-cell lymphomas (PTCL).

"Patients with advanced mycosis fungoides and Sézary syndrome often face a poor prognosis and limited treatment options after multiple prior lines of therapy," said Prof. Pierluigi Porcu, Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia and principal investigator of the TELLOMAK trial. "The durability and depth of responses observed with lacutamab in this study are highly promising and represent a significant advancement for this patient population."

"The long-term follow-up data from the TELLOMAK clinical study confirms lacutamab’s meaningful clinical benefit in Sézary syndrome and mycosis fungoides and were the basis of the FDA Breakthrough Therapy Designation. We are encouraged by these results and are actively preparing a Phase 3 trial in collaboration with health authorities to bring this promising therapy to patients as swiftly as possible," added Dr Sonia Quaratino, Chief Medical Officer of Innate Pharma.

1 Compared to results previously presented at ASH (Free ASH Whitepaper) 2023 and ASCO (Free ASCO Whitepaper) 2024.

Efficacy results in SS patients (Data cut-off: OCT 17, 2024)

Best Response

Global
N=63

in Skin
N=63

in Blood
N=63

in Lymph Nodes
N=52*

CR (complete response), N (%)

6 (9.5)

9 (14.3)

21 (33.3)

9 (17.3)

PR (partial response), N (%)

21 (33.3)

24 (38.1)

11 (17.5)

6 (11.5)

SD (stable disease), N (%)

28 (44.4)

27 (42.9)

26 (41.3)

27 (51.9)

PD (progressive disease), N (%)

8 (12.7)

3 (4.8)

5 (7.9)

6 (11.5)

NE (not evaluable), N (%)

4 (7.7)

ORR, % [95% CI]

42.9

[31.4-55.1]

52.4

[40.3-64.2]

50.8

[38.8-62.7]

28.8

[18.3-42.3]

Time to response, months, median (range)

2.8 (1-10)

DoR, months, median [95% CI]

25.6

[11.0 – NE]

PFS, months, median [95% CI]

8.3

[5.1-18.7]

Efficacy results in MF patients (Data cut-off: OCT 17, 2024)

Best Response

All MF

N=107

KIR3DL2 ≥1%

N=48

KIR3DL2 <1%

N=59

CR (complete response), N (%)

3 (2.8)

3 (6.3)

0 (0.0)

PR (partial response), N (%)

18 (16.8)

7 (14.6)

11 (18.6)

SD (stable disease), N (%)

71 (66.4)

30 (62.5)

41 (69.5)

PD (progressive disease), N (%)

13 (12.1)

6 (12.5)

7 (11.9)

ORR (Objective Response Rate), % [95%CI] Olsen 2011

19.6 [13.2, 28.1]

20.8 [11.7, 34.3]

18.6 [10.7, 30.4]

ORR, % [95%CI] Olsen 2022

24.3 [17.2, 33.2]

29.2 [18.2, 43.2]

20.3 [12.0, 32.3]

Time to response, months, median (range)

2.8 (1-37)

1.0 (1-5)

2.8 (1-37)

DoR, months, median [95% CI]

13.8 [7.4, NE]

13.8 [4.6, NE]

15.7 [5.1, NE]

PFS, months, median [95% CI]

10.2 [8.0, 15.4]

11.8 [5.6, 16.8]

9.5 [6.5, 16.6]

Abstract details:

Abstract: 2522

Abstract Title: Lacutamab in patients with relapsed and refractory Sézary syndrome: Long term follow-up from the TELLOMAK phase 2 trial

Session Type: Poster Session

Session Title: Developmental Therapeutics—Immunotherapy

Session Date and Time: Monday June 2, 2025 – 1:30 – 4:30 PM CDT

Abstract: 2523

Abstract Title: Lacutamab in patients with relapsed and/or refractory mycosis fungoides: Long-term follow-up and translational data from the TELLOMAK phase 2 trial

Session Type: Poster Session

Session Title: Developmental Therapeutics—Immunotherapy

Session Date and Time: Monday June 2, 2025 – 1:30 – 4:30 PM CDT

About Lacutamab

Lacutamab is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease, and peripheral T cell lymphoma (PTCL). Rare cutaneous lymphoma of T lymphocytes have a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up to 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. KIR3DL2 is expressed in up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

Lacutamab has been granted European Medicines Agency (EMA) PRIME designation, and the US Food and Drug Administration (FDA) granted Fast Track designation for the treatment of patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. Lacutamab is granted orphan drug status in the European Union and the United States for the treatment of CTCL. Lacutamab has received Breakthrough Therapy Designation from the FDA.

About TELLOMAK

TELLOMAK (NCT03902184) is a global, open-label, multi-cohort Phase 2 clinical trial in patients with Sézary syndrome and mycosis fungoides (MF) in the United States and Europe. Specifically:

Cohort 1: lacutamab being evaluated as a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication.
Cohort 2: lacutamab being evaluated as a single agent in patients with MF that express KIR3DL2, as determined at baseline with a Simon 2-stage design.
Cohort 3: lacutamab being evaluated as a single agent in patients with MF that do not express KIR3DL2, as determined at baseline, with a Simon-2 stage design.
All comers: lacutamab being evaluated as a single agent in patients with both KIR3DL2 expressing and non-expressing MF to explore the correlation between the level of KIR3DL2 expression and treatment outcomes utilizing a formalin-fixed paraffin embedded (FFPE) assay under development as a companion diagnostic.
The trial is fully enrolled. The primary endpoint of the trial is objective global response rate. Key secondary endpoints are progression-free survival, duration of response, overall survival, quality of life, pharmacokinetics and immunogenicity and adverse events.

City of Hope Researchers to Present Cancer Advances That Could Boost Survival at the American Society of Clinical Oncology (ASCO) Annual Meeting

On May 22, 2025 Researchers from City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States with its National Medical Center named Top 5 "Best Hospital" in the nation for cancer care by U.S. News & World Report, reported that it will present novel cancer treatment approaches and combinations, leading-edge targeted therapies, and supportive care interventions that could reduce cancer risk and improve survival at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 30 to June 3 in Chicago and online (Press release, City of Hope, MAY 22, 2025, View Source [SID1234653348]).

This year’s ASCO (Free ASCO Whitepaper) meeting unites nearly 45,000 oncology professionals to discuss leading-edge scientific data and attend educational sessions, empowering health care teams to deliver more personalized and effective lifesaving cancer care to patients.

Highlights of City of Hope’s ASCO (Free ASCO Whitepaper) data include the below, which focus on breast, genitourinary and gastrointestinal cancers.

1015: Real-world data show it is safe to readminister trastuzumab-deruxtecan to metastatic breast cancer patients who experience low-grade lung complications
Attend: Friday, May 30 at 2:57 p.m. CDT in Hall D2

A large, multicenter retrospective study further supports the safety of readministering the antibody-drug conjugate trastuzumab-deruxtecan (T-DXd) to metastatic breast cancer patients after initial drug pauses due to low-grade interstitial lung disease (ILD), which is defined as radiographic evidence of lung inflammation without associated symptoms.

T-DXd is approved for HER2+ and HER2-low and ultra-low advanced breast cancer as well as for many other solid tumors. It carries a rare but serious risk of ILD, requiring frequent imaging and symptom evaluation. Guidelines recommend permanent discontinuation for grade 2 (symptomatic) or higher ILD, but physicians can choose to readminister T-DXd to patients with asymptomatic grade 1 ILD after resolution of imaging findings.

This real-world data of 712 metastatic breast cancer patients treated with T-DXd is significant because limited data exists on the outcomes of readministering T-DXd or "rechallenge" after ILD. The only other dataset included a pooled analysis of nine clinical trials and was presented by Hope S. Rugo, M.D., F.A.S.C.O., City of Hope Women’s Cancers Program director; professor, Department of Medical Oncology & Therapeutics Research, at the 2024 ESMO (Free ESMO Whitepaper) Breast Cancer Annual Congress. This pooled data was recently submitted for publication.

"The real-world data shows that patients with metastatic breast cancer who were treated with trastuzumab-deruxtecan experienced prolonged clinical benefit even if it had to be discontinued temporarily due to low-grade interstitial lung disease. Importantly, patients treated with steroids had faster radiographic ILD improvement, highlighting the importance of early steroid use," said, Dr. Rugo, corresponding author of the ASCO (Free ASCO Whitepaper) abstract.

The researchers collected patient demographics, T-DXd and steroid dosing, imaging results, and outcomes after rechallenge. About 9% of the study’s patients experienced ILD at some level. Some 47 patients were rechallenged — 81% after grade 1 ILD. Among the patients with grade 1 ILD, 56% received steroids for a median of 36 days. Radiographic improvement was seen at a median of 24 days for patients treated with steroids vs. 82 days for those who did not receive steroids.

Among patients rechallenged after grade 1 ILD, recurrent ILD rates were low, with the majority being grade 1. None were grade 5. After rechallenge, patients remained on T-DXd for a median of 215 days. About 26% developed recurrent ILD at a median of 211 days from rechallenge.

4510: Tracking the genomic evolution of kidney cancer and recurrence to identify biomarkers of care
Attend: Saturday, May 31 at 4:54 p.m. CDT in the Arie Crown Theater

Some 20% of renal cell carcinoma (RCC) patients who undergo curative kidney cancer surgery experience disease recurrence. Experts have evaluated in a Phase 3 trial (IMmotion010) whether administering monoclonal antibody atezolizumab post-surgery could prevent RCC from returning and found that it did not.

However, a precision medicine study led by City of Hope’s Sumanta Kumar Pal, M.D., F.A.S.C.O., found that patients who had specific genomic biomarkers in that Phase 3 trial experienced longer disease-free survival when atezolizumab was used after kidney resection.

"We continue to investigate the genetics of kidney cancer patients to understand how we can use this information to prolong life. This study builds on a biomarker, KIM-1, that can identify RCC patients who benefit from adjuvant atezolizumab by using tumor-based genomic features," said Dr. Pal, City of Hope professor, Department of Medical Oncology & Therapeutics.

In the study, the researchers obtained pretreatment tumor tissue samples from 754 patients. Qualifying patient samples were categorized into seven molecular subgroups and further split as biomarker KIM-1 high or KIM-1 low. The scientists found that patients in cluster 6 (stromal/proliferative) appeared to benefit from atezolizumab (n=50). Additionally, patients with KIM-1-high biomarkers and more Teff cells responsible for facilitating immune responses were linked to longer disease-free survival when adjuvant atezolizumab was administered.

"KIM-1 is the most robust predictor of outcome with atezolizumab. We performed whole transcriptome sequencing of RCC tumors before using atezolizumab as well as at disease recurrence, when able, and spotlighted a genomic evolution in disease progression that offers insights into why patients with RCC relapse. Further defining these biomarkers will allow oncologists to provide more personalized care to kidney cancer patients," said Dr. Pal, who is a paid consultant to Roche, the manufacturer of atezolizumab.

3553: A combination treatment of checkpoint inhibitors Vilastobart and atezolizumab shows promise in patients with advanced colorectal cancer
Visit: Saturday, May 31, from 9 a.m. to noon CDT in Hall A

In Phase 2 of a safety and tolerability clinical trial, metastatic colorectal cancer patients who have microsatellite stability (MSS) demonstrated initial evidence of anti-tumor activity when treated with the checkpoint inhibitors Vilastobart (XTX101) and atezolizumab. About 96% of metastatic colorectal cancer cases are MSS.

"This finding is noteworthy because we are seeing a novel combination therapy shrink tumors in a patient population with advanced solid tumors that historically have been nonresponsive to immune checkpoint inhibitors," said Marwan Fakih, M.D., City of Hope professor, Department of Medical Oncology & Therapeutics Research, and lead author of the abstract.

As of this January, 40 patients with MSS colorectal cancer were dosed in Phase 2 of the trial. About 70% of patients had had three or more prior lines of therapy. Those who were previously treated with a type of immune checkpoint inhibitor were excluded.

On the Phase 2 trial, 27% of patients without liver metastatic disease experienced a partial response, defined as more than 50% shrinkage of target lesions. Patients with tumor shrinkage had a significant decrease in circulating tumor DNA, further confirming the clinical efficacy of this combination. The combination was safe as it was associated with a low rate of severe immune-related complications. The safety was further demonstrated by a very low rate of treatment discontinuation.

Vilastobart is an investigational checkpoint inhibitor being developed by Xilio Therapeutics, a company licensing City of Hope technology and co-founded by City of Hope’s Dr. John Williams. Dr. Fakih is a paid advisory board member of Xilio Therapeutics.

5041: Using real-world data to provide insights into treatment that has a lower chance of causing heart attack and stroke in prostate cancer patients
Visit: Monday, June 2, from 9 a.m. to noon CDT in Hall A

A study led by City of Hope’s Alan H. Bryce, M.D., provides decision-making insights to aid with the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), especially those at high risk of cardiovascular events like heart failure and stroke.

The study used real-world data to confirm clinical trial findings which suggest mCRPC patients who have never had chemotherapy and were treated with testosterone blocker abiraterone acetate have a higher risk of hospitalization due to cardiovascular events than patients treated with androgen receptor inhibitor enzalutamide.

Dr. Bryce led a group of scientists who analyzed the data of more than 68 million seniors who are U.S. Medicare and Medicaid beneficiaries. They included mCRPC patients who were 65 or older and have never had chemotherapy. Patients were then stratified into subgroups based on cardiovascular disease history.

People treated with abiraterone acetate had a statistically significant higher risk of experiencing cardiovascular events like heart attacks, strokes, coronary revascularization to restore blood flow, heart failure, irregular heart rhythm and blood clots compared to mCRPC patients treated with enzalutamide. Additionally, the researchers found that the risk of death was higher with abiraterone acetate than with enzalutamide regardless of cardiovascular disease history.

"Real-world data studies like this one are crucial because they provide a broader, more representative perspective on health and disease compared to data from clinical trials, which usually are conducted in controlled settings. Large data sets allow for deeper understanding of how treatments affect patients in real-life scenarios and includes factors not captured in carefully designed clinical trials," said Dr. Bryce, who is a paid speaker for Pfizer, the manufacturer of enzalutamide.

MiraDx Announces New Research Conducted in Collaboration with UCLA and Accepted for Presentation at ASCO 2025 that Highlights the Role of MicroRNA-based Genetic Signatures in Predicting Radiation and Immunotherapy Treatment-Related Outcomes

On May 22, 2025 MiraDx, a molecular diagnostics company advancing germline-based personalization of cancer treatment, reported two studies will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 30 to June 3 in Chicago, IL (Press release, UCLA Technology Development Group, MAY 22, 2025, View Source [SID1234653347]). The studies, run in partnership with UCLA, highlight MiraDx’s platform as a predictive tool for treatment toxicity and response to modern cancer immunotherapies.

"Toxicity from cancer therapies remains one of the most difficult challenges patients face, disrupting treatment, diminishing quality of life, and creating uncertainty at every step," said Joanne Weidhaas, MD, PhD, professor of radiation oncology and vice chair of molecular and cellular oncology at the David Geffen School of Medicine at UCLA and co-founder of MiraDx. "As cancer therapies become more targeted and complex, we need predictive tools based on personal patient genetics that identify who is at increased risk for treatment-related adverse events and toxicities. This same class of genetics can also indicate how they will respond to therapy. Research to be presented at ASCO (Free ASCO Whitepaper) 2025 in radiation treatment for soft tissue sarcoma and anti-PD1 therapies further demonstrate the robust accuracy of mirSNPs to give patient specific information that could guide treatment decisions that balance efficacy with long-term quality of life."

Poster Presentation #21 (Abstract #11538): Personalized Radiation Strategies in Soft Tissue Sarcoma

Title: MicroRNA-based Biomarkers of Outcome in Soft Tissue Sarcoma Treated with Hypofractionated Preoperative Radiation Therapy
Poster Session: Sarcoma
Date/Time: May 31, 9:00 AM CDT
Location: Hall A—Posters and Exhibits

Overview: Response to radiation in soft tissue sarcoma (STS) is highly variable, complicating treatment optimization. Building on prior research, this study analyzes a larger cohort treated with preoperative hypofractionated radiation therapy (SBRT) to assess the predictive value of germline mirSNPs (microRNA SNPs) for certain treatment-related outcomes. Preliminary genetic signatures were found to predict major wound toxicity, late toxicity, distant metastases, and pathological response, which points to the potential for mirSNPs to guide more personalized treatment strategies and decision-making regarding treatment regimens.

Poster Presentation #308 (Abstract #2661): Predicting Immune-Related Toxicity from Anti-PD1 Therapy

Title: MicroRNA-based Signatures of Early and Late Immune-Related Adverse Events to anti-PD1 Treatment
Poster Session: Developmental Therapeutics—Immunology
Date/Time: June 2, 1:30 PM CDT
Location: Hall A—Posters and Exhibits

Overview: As immune checkpoint inhibitors (ICIs) continue to reshape cancer treatment, predicting immune-related adverse events (irAEs) presents ongoing challenges. This study builds on earlier work by analyzing an expanded cohort, uncovering key genetic differences associated with cycle-specific toxicities in patients treated with anti-PD1 as well as treatment response. Enhanced models for early and late irAEs demonstrate strong predictive risk, confirming the potential of microRNA-based signatures to be applied to improve the safety of ICIs.

Meet the Investigator

Dr. Joanne Weidhaas, co-founder of MiraDx and professor at the David Geffen School of Medicine and head of translational research in the Department of Radiation Oncology at UCLA, will present both posters and discuss implications for personalized cancer therapy.

Daiichi Sankyo Continues to Transform Treatment Landscape for Patients with Cancer with Practice-Changing Data at ASCO

On May 22, 2025 Daiichi Sankyo (TSE: 4568) reported it will present new clinical research across its oncology portfolio with more than 20 abstracts in multiple cancers at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Scientific Program (#ASCO25) (Press release, Daiichi Sankyo, MAY 22, 2025, https://www.businesswire.com/news/home/20250522174780/en/Daiichi-Sankyo-Continues-to-Transform-Treatment-Landscape-for-Patients-with-Cancer-with-Practice-Changing-Data-at-ASCO [SID1234653346]).

Data at ASCO (Free ASCO Whitepaper) showcasing the company’s progress towards creating new standards of care for patients with cancer will include two late-breaking oral presentations. The first will feature results of the DESTINY-Breast09 phase 3 trial (LBA #1008) where ENHERTU (trastuzumab deruxtecan) in combination with pertuzumab demonstrated superior progression-free survival compared to taxane, trastuzumab and pertuzumab (THP) as a first-line treatment in patients with HER2 positive metastatic breast cancer. The second will highlight results of the DESTINY-Gastric04 phase 3 trial (LBA #4002) where ENHERTU demonstrated superior overall survival compared to ramucirumab and paclitaxel as a second-line treatment in patients with HER2 positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Data from DESTINY-Breast09 and DESTINY-Gastric04 will be featured in ASCO (Free ASCO Whitepaper) press briefings.

"This year’s ASCO (Free ASCO Whitepaper) marks the fourth in a row where potential practice-changing ENHERTU data will be showcased," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "With the results of DESTINY-Breast09 and DESTINY-Gastric04, we now have six breast and two gastric cancer randomized trials that have demonstrated significant survival improvements with ENHERTU. These data, along with other updates across our industry-leading oncology portfolio, underscore our commitment to pushing the boundaries of science to create new medicines or combination strategies that improve outcomes for patients with cancer."

Other ENHERTU data at ASCO (Free ASCO Whitepaper) will include an oral presentation featuring an exploratory circulating tumor DNA analysis of the DESTINY-Breast06 phase 3 trial (#1013) evaluating ENHERTU compared to physician’s choice of chemotherapy in hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) metastatic breast cancer. Updated results from the PRO-DUCE study (#1545) examining vital sign monitoring compared to usual care in patients with metastatic breast cancer receiving ENHERTU also will be highlighted as a poster presentation.

A trials-in-progress poster presentation will feature the DESTINY-Gastric05 phase 3 trial (TPS4207) evaluating ENHERTU in combination with a fluoropyrimidine-based chemotherapy and pembrolizumab compared to trastuzumab in combination with platinum-based chemotherapy and pembrolizumab in previously untreated patients with unresectable, locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or GEJ cancer.

Progress in Lung Cancer Across Daiichi Sankyo’s DXd ADC Portfolio
Updated DATROWAY (datopotamab deruxtecan) combination data across three early-phase trials will be highlighted in patients with early or advanced non-small cell lung cancer (NSCLC).

Updated results from the TROPION-Lung02 phase 1b trial (#8501) evaluating DATROWAY plus pembrolizumab with or without platinum-based chemotherapy in patients with previously untreated advanced NSCLC without actionable genomic alterations will be featured as an oral presentation. This will include results from an exploratory analysis using quantitative continuous scoring (QCS), AstraZeneca’s proprietary computational pathology platform.

Poster sessions will highlight the first presentation of data of DATROWAY and rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, from the TROPION-Lung04 phase 1b trial (#8521) cohort evaluating the combination in patients without actionable genomic alterations who have advanced or metastatic NSCLC, and the final pathologic complete response and major pathologic response data from the NeoCOAST-2 phase 2 trial (#8046) evaluating DATROWAY with durvalumab, AstraZeneca’s anti-PD-L1 therapy, and chemotherapy as neoadjuvant treatment followed by adjuvant treatment with durvalumab in patients with resectable early-stage (IIA to IIIB) NSCLC.

Additional lung cancer data at ASCO (Free ASCO Whitepaper) will include an oral presentation of the HERTHENA-Lung02 phase 3 trial (#8506) of patritumab deruxtecan (HER3-DXd) versus platinum doublet chemotherapy in patients with locally advanced or metastatic EGFR-mutated NSCLC with disease progression following the use of an EGFR tyrosine kinase inhibitor (TKI).

Trials-in-progress poster presentations in lung cancer across the DXd ADC portfolio will include the TROPION-Lung14 phase 3 trial (TPS8647) evaluating DATROWAY combined with osimertinib, AstraZeneca’s EGFR TKI, compared to osimertinib alone in the first-line setting of patients with locally advanced or metastatic EGFR-mutated NSCLC and a substudy of KEYMAKER-U01, a phase 1/2 trial (TPS8652), evaluating pembrolizumab plus ifinatamab deruxtecan (I-DXd) or patritumab deruxtecan with or without chemotherapy in patients with untreated advanced NSCLC.

Additional Data and Trials-in-Progress Across Daiichi Sankyo’s Oncology Portfolio at ASCO (Free ASCO Whitepaper)
Oral presentations also will highlight initial results from the TUXEDO-3 phase 2 trial (#2005) evaluating patritumab deruxtecan in patients with metastatic breast cancer or advanced NSCLC and active brain metastases and in patients with leptomeningeal carcinomatosis/disease from advanced solid tumors, as well as results from a phase 1 trial (#10003) evaluating valemetostat, a dual EZH1 and EZH2 inhibitor, in pediatric patients with malignant solid tumors.

Additional DXd ADC trials-in-progress poster presentations include the REJOICE-PanTumor01 phase 2 trial (TPS3158) evaluating raludotatug deruxtecan (R-DXd) in patients with locally advanced or metastatic gynecologic or genitourinary cancers, IDeate-PanTumor02 phase 1b/2 trial (TPS3157) evaluating ifinatamab deruxtecan in patients with recurrent or metastatic solid tumors and a substudy of KEYMAKER-U06, a phase 1/2 trial (TPS4209) evaluating ifinatamab deruxtecan in combination with pembrolizumab with or without chemotherapy in patients with advanced esophageal squamous cell carcinoma. Other trials-in-progress posters include the QuANTUM-Wild phase 3 trial (TPS6580) evaluating VANFLYTA (quizartinib) in combination with chemotherapy in patients with FLT3-ITD negative acute myeloid leukemia and a first-in-human phase 1 trial of DS-2243 (TPS2668), a potential first-in-class bispecific T-cell engager targeting HLA-A*02/NY-ESO in patients with advanced solid tumors.

Daiichi Sankyo will hold a virtual conference call for investors on Monday, June 2, 2025 from 6:00 to 7:15 pm CDT / Tuesday, June 3, 2025 from 8:00 to 9:15 am JST. Executives from Daiichi Sankyo will provide an overview of the ASCO (Free ASCO Whitepaper) research data and address questions.

Details of the two late-breaking ENHERTU oral presentations at ASCO (Free ASCO Whitepaper) 2025 include:

Presentation Title

Author

Abstract

Presentation (CDT)

LBAs

Trastuzumab deruxtecan (T-DXd) + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) for first-line treatment of patients with human epidermal growth factor receptor 2 positive (HER2+) advanced/metastatic breast cancer: interim results from DESTINY-Breast09

S. Tolaney

LBA1008

Special LBA Session

Oral Presentation

Monday, June 2

7:30 – 8:00 am

Trastuzumab deruxtecan (T-DXd) vs ramucirumab plus paclitaxel in second-line treatment of patients with human epidermal growth factor receptor 2 positive (HER2+) unresectable/metastatic gastric cancer or gastroesophageal junction adenocarcinoma: primary analysis of the randomized, phase 3 DESTINY-Gastric04 study

K. Shitara

LBA4002

Oral Presentation

Saturday, May 31

3:00 – 6:00 pm

Highlights of additional clinical data and trials-in-progress from Daiichi Sankyo’s oncology pipeline include:

Presentation Title

Author

Abstract

Presentation (CDT)

Breast

Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy in HER2 low/ultralow, hormone receptor-positive (HR+) metastatic breast cancer in DESTINY-Breast06

R. Dent

1013

Oral Presentation

Saturday, May 31

1:15 – 4:15 pm

HERTHENA-Breast03: a phase 2, randomized, open-label study evaluating neoadjuvant patritumab deruxtecan + pembrolizumab before or after pembrolizumab + chemotherapy for early-stage TNBC or HR-low+/HER2- breast cancer

O’Shaughnessy

TPS629

Poster Session

Monday, June 2

9:00 am – 12:00 pm

Electronic patient-reported outcomes with vital sign monitoring versus usual care during trastuzumab deruxtecan treatment for metastatic breast cancer: updated results from the PRO-DUCE study

Y. Kikawa

1545

Poster Session

Sunday, June 1

9:00 am – 12:00 pm

Lung

TROPION-Lung02: datopotamab deruxtecan (Dato-DXd) plus pembrolizumab with or without platinum chemotherapy as first-line therapy for advanced non-small cell lung cancer

B. Levy

8501

Oral Presentation

Sunday, June 1

8:00 – 11:00 am

Patritumab deruxtecan (HER3-DXd) in resistant EGFR-mutated advanced non-small cell lung cancer after a third-generation EGFR TKI: the phase 3 HERTHENA-Lung02 study

T. Mok

8506

Oral Presentation

Sunday, June 1

8:00 – 11:00 am

First-line datopotamab deruxtecan (Dato-DXd) + rilvegostomig in advanced or metastatic non-small cell lung cancer: results from TROPION-Lung04 (cohort 5)

S. Waqar

8521

Poster Session

Saturday, May 31

1:30 – 4:30 pm

TROPION-Lung14: a phase 3 study of osimertinib ± datopotamab deruxtecan (Dato-DXd) as first-line treatment for patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer

S. Lu

TPS8647

Poster Session

Saturday, May 31

1:30 – 4:30 pm

Neoadjuvant durvalumab + chemotherapy + novel anticancer agents and adjuvant durvalumab ± novel agents in resectable non-small cell lung cancer: updated outcomes from NeoCOAST-2

T. Cascone

8046

Poster Session

Saturday, May 31

1:30 – 4:30 pm

KEYMAKER-U01 substudy 01A: phase 1/2 study of pembrolizumab plus ifinatamab deruxtecan (I-DXd) or patritumab deruxtecan (HER3-DXd) with or without chemotherapy in untreated stage IV non-small cell lung cancer

C. Aggarwal

TPS8652

Poster Session

Saturday, May 31 1:30 – 4:30 pm

Gastric

An open-label, randomized, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) + chemotherapy ± pembrolizumab versus chemo + trastuzumab ± pembro in first-line metastatic HER2+ gastric or gastroesophageal junction cancer: DESTINY-Gastric05

K. Shitara

TPS4207

Poster Session

Saturday, May 31

9:00 am – 12:00 pm

Esophageal

KEYMAKER-U06 substudy 06E: phase 1/2 open-label, umbrella platform study of ifinatamab deruxtecan in combination with pembrolizumab with or without chemotherapy for first-line treatment of advanced esophageal squamous cell carcinoma

K. Kato

TPS4209

Poster Session

Saturday, May 31

9:00 am – 12:00 pm

AML

QuANTUM-Wild: a phase 3, randomized, double-blind, placebo-controlled trial of quizartinib in combination with chemotherapy and as single-agent maintenance in FLT3-ITD negative acute myeloid leukemia

P. Montesinos

TPS6580

Poster Session

Sunday, June 1

9:00 am – 12:00 pm

Pan-Tumor

Patritumab deruxtecan (HER3-DXd) in active brain metastases from metastatic breast and non-small cell lung cancers, and leptomeningeal disease from advanced solid tumors: results from the TUXEDO-3 phase 2 trial

M. Preusser

2005

Oral Presentation

Friday, May 30

2:45 – 5:45 pm

IDeate-PanTumor02: a phase 1b/2 study to evaluate the efficacy and safety of ifinatamab deruxtecan (I-DXd) in patients with recurrent or metastatic solid tumors

T. Kogawa

TPS3157

Poster Session

Monday, June 2

1:30 – 4:30 pm

REJOICE- PanTumor01: a phase 2 signal-seeking study of raludotatug deruxtecan (R-DXd) in patients with advanced or metastatic gynecologic or genitourinary tumors

L. Albiges

TPS3158

Poster Session

Monday, June 2

1:30 – 4:30 pm

A phase 1, first-in-human study of DS-2243, an HLA-A*02/NY-ESO directed bispecific T‑cell engager, in patients with advanced solid tumors

S. D’Angelo

TPS2668

Poster Session

Monday, June 2

1:30 – 4:30 pm

Pediatric

Safety and efficacy of the EZH1/2 inhibitor valemetostat tosylate (DS-3201b) in pediatric patients with malignant solid tumors (NCCH1904): a multicenter phase 1 trial

A. Arakawa

10003

Oral Presentation

Saturday, May 31

3:00 – 6:00 pm