On October 19, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported results from the Phase III HARMONi-6 trial, conducted in China and sponsored by our partner, Akeso, Inc. (HKEX Code: 9926.HK), featuring the novel, potential first-in-class investigational bispecific antibody, ivonescimab. The data was presented today as part of the Presidential Symposium at the European Society for Medical Oncology 2025 Congress (ESMO 2025) in Berlin, Germany.

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The HARMONi-6 presentation, Phase III Study of Ivonescimab plus chemotherapy versus Tislelizumab plus chemotherapy as First-line Treatment for advanced squamous non-small cell lung cancer (HARMONi-6), evaluated ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) irrespective of PD-L1 expression. HARMONi-6 is a single region, multi-center, Phase III study conducted in China sponsored by Akeso with all relevant data exclusively generated, managed, and analyzed by Akeso.

The trial results were presented by Dr. Shun Lu, MD, PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital, Professor of Medicine at Shanghai Jiaotong University, and associate editor for the Journal of Thoracic Oncology.

In major markets globally, first-line therapy for patients with advanced non-small cell lung cancer without driver mutations is most commonly a PD-1 inhibitor plus platinum-based chemotherapy. Prior to HARMONi-6, there were no known Phase III clinical trials in advanced NSCLC which have shown a statistically significant and clinically meaningful improvement compared to PD-(L)1 inhibitor therapy in combination with chemotherapy in a head-to-head setting.

Clinically Meaningful Efficacy

In the HARMONi-6 planned interim analysis of progression-free survival (PFS), ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint, PFS, by Independent Radiologic Review Committee (IRRC), when compared to tislelizumab in combination with chemotherapy, achieving a hazard ratio (HR) of 0.60 (95% CI: 0.46, 0.78; p<0.0001). A clinically meaningful benefit was demonstrated across clinical subgroups, including those with either PD-L1 negative or positive expression. Both the overall response rate (ORR) measured according to RECIST v1.1 criteria, as well as the duration of response (DoR) were higher in patients treated with ivonescimab plus chemotherapy compared to those treated with tislelizumab plus chemotherapy.

HARMONi-6 ITT (n=532):

Ivonescimab + Chemo

Tislelizumab + Chemo

Median Follow-up: 10.28 mos

(n=266)

(n=266)

Median PFS

11.14 mos

(95% CI: 9.86, NE)

6.90 mos

(95% CI: 5.82, 8.57)

PFS Stratified HR

0.60

(95% CI: 0.46, 0.78; p<0.0001)

ORR

75.9%

66.5%

DoR

11.20 mos

(95% CI: 8.54, NE)

8.38 mos

(95% CI: 5.72, NE)

ITT: Intention-to-Treat population; mos.: months; NE: not established

HARMONi-6 PD-L1 Subgroup Analyses

Ivonescimab + Chemo vs.

Tislelizumab + Chemo

PD-L1 Negative (PD-L1 TPS <1%) PFS stratified HR

0.55

Ivonescimab + Chemo n=105; Tislelizumab + Chemo n=105

(95% CI: 0.37, 0.82)

PD-L1 Positive (PD-L1 TPS >1%) PFS stratified HR

0.66

Ivonescimab + Chemo n=161; Tislelizumab + Chemo n=161

(95% CI: 0.46, 0.95)

Overall survival (OS) data was not yet mature at the time of the data cutoff and will be evaluated in the future.

Manageable Safety Profile

Ivonescimab demonstrated an acceptable and manageable safety profile in the HARMONi-6 study, which was consistent with previous Phase III studies conducted studying ivonescimab.

In squamous NSCLC, VEGF-A monoclonal antibodies have not been approved by health authorities including the FDA and have had limited clinical development based on historical early phase clinical trials, primarily due to significant risks of toxicity, including hemorrhage and other life-threatening, bleeding-related complications. The results of this study further validate the unique mechanism of action of ivonescimab, including key differences as compared to separately administering an anti-PD-1 monoclonal antibody and an anti-VEGF monoclonal antibody.

In this Phase III study, there were nine patients (3.4%) who discontinued ivonescimab plus chemotherapy due to treatment-related adverse events (TRAEs) compared to 11 patients (4.2%) who discontinued tislelizumab plus chemotherapy due to TRAEs. There were eight patients (3.0%) in the ivonescimab plus chemotherapy arm and 10 patients (3.8%) in the tislelizumab plus chemotherapy arm who died as a result of TRAEs in this Phase III study. The most frequent TRAEs for ivonescimab treatment in combination with chemotherapy were common chemotherapy-related AEs, including alopecia, anemia, and various laboratory abnormalities, including neutrophil, white blood cell, and platelet count decreases. Grade 3 or higher immune-related adverse events occurred in 9.0% of patients receiving ivonescimab in combination with chemotherapy and 10.2% of patients receiving tislelizumab in combination with chemotherapy. Grade 3 or higher adverse events that were possibly VEGF-related in the ivonescimab plus chemotherapy arm were 7.5% vs. 2.3% for tislelizumab plus chemotherapy. Most of the possibly VEGF-related adverse events occurring in the ivonescimab plus chemotherapy arm were classified as Grade 1 or 2. Of note, Grade 3 or higher hemorrhage events were observed in five patients in the ivonescimab plus chemotherapy arm compared to two patients in the tislelizumab plus chemotherapy arm in this study.

HARMONi-6

Ivonescimab + Chemo

(n=266)

Tislelizumab + Chemo

(n=265)

Serious TRAEs (TRSAEs)

32.3%

30.2%

TRAEs Leading to Drug Discontinuation

3.4%

4.2%

TRAEs Leading to Death

3.0%

3.8%

Grade 3+ Immune-related

9.0%

10.2%

Grade 3+ Possibly VEGF-related*

7.5%

2.3%

*In the ivonescimab plus chemotherapy arm, possibly VEGF-related Grade 3+ events were largely driven by conditions such as hypertension (3.0%) and proteinuria (2.3%) and largely did not lead to the discontinuation of ivonescimab. TRAE: treatment-related adverse event

"The novel mechanism of action of ivonescimab may allow for an improved clinical profile and longer duration of therapy, which help improve outcomes – this distinguishes ivonescimab from other PD-1 monoclonal antibodies and PD-(L)1 plus VEGF treatments administered separately," added Dr. Maky Zanganeh, Co-Chief Executive Officer and President of Summit. "No more striking is this result than in squamous NSCLC where the benefit of anti-VEGF therapy has been largely unrealized. Combined with the improved benefit in patients across all levels of PD-L1 expression, implying a true improvement in the immunotherapy activity, this study of ivonescimab in combination with chemotherapy provides rich context as to the potential benefit of ivonescimab across solid tumors, reaffirming its incredible potential to help a wide variety of patients suffering from cancer."

HARMONi-6 Clinical Trial Results Published in The Lancet

Today The Lancet published a manuscript titled, "Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial." The publication is based on the results of HARMONi-6, a single region, multi-center, Phase III study conducted in China sponsored by Akeso, with data generated and analyzed by Akeso.

"HARMONi-6 is yet another meaningful milestone for ivonescimab, Team Summit, and our partners at Akeso, and most importantly, continues to advance a potential treatment option for patients living with difficult-to-treat cancers," said Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. "We remain extraordinarily proud of our partnership with Akeso and their ongoing clinical accomplishments and advancement of ivonescimab in solid tumors. We also would like to express our heartfelt appreciation to those physicians and patients in China who participated in this important study, who are helping to advance the treatment of patients around the world with this incredibly innovative therapy."

HARMONi-3 Clinical Trial Update

Summit is currently enrolling patients in the HARMONi-3 study. HARMONi-3 is a multiregional Phase III clinical trial sponsored by Summit which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC. HARMONi-3 is currently enrolling patients globally and is conducted with registrational intent for the United States and other regions within Summit’s license territories. The dual primary endpoints for this study are PFS and OS.

Summit has amended the protocol for the HARMONi-3 study in order to separate the statistical analysis (i.e., the outcome) of the primary endpoints by histology. Therefore, there will be separate analyses conducted to evaluate ivonescimab plus chemotherapy compared to pembrolizumab plus chemotherapy in patients with squamous NSCLC and in patients with non-squamous NSCLC.

As a result of having two separate intention-to-treat analyses within the HARMONi-3 study, the analyses for squamous tumors and non-squamous tumors may be conducted at separate times, as each analysis will be conducted upon the prespecified numbers of events being reached in the separate cohorts.

Summit currently expects to complete enrollment in the squamous cohort of HARMONi-3 in the first half of 2026 and expects to reach the prespecified number of events for the PFS primary endpoint analysis for this cohort in the second half of 2026. An interim analysis for overall survival may be conducted at a similar time.

At present time, Summit expects to complete enrollment in the non-squamous cohort of HARMONi-3 in the second half of 2026 and expects to reach the prespecified number of events for the PFS primary endpoint analysis for this cohort in the first half of 2027. An interim analysis for overall survival is planned to be conducted based upon reaching a prespecified number of events.

In order to sufficiently power each of the dual primary endpoints in both cohorts of this study, Summit plans to enroll 600 patients with squamous NSCLC and 1,000 patients with non-squamous NSCLC.

Reference Comparison of Results of 1L Squamous NSCLC Studies Evaluating Pembrolizumab or Tislelizumab Plus Chemotherapy Compared to Chemotherapy

Study Data at

Initial Readout

Study Regions

Median PFS

(PD-1 +

Chemo Arm)

Hazard Ratio

vs. Chemo*

Median

Follow-up

Time

Source

KEYNOTE-407

(n=559)

Multiregional Study

6.4 months

HR=0.56

7.8 months

Paz-Ares, NEJM, 2018

RATIONALE-307

(n=360)

China Regional Study

7.6 months

HR=0.52*

8.6 months

Wang, JAMA Oncology, 2021

*RATIONALE-307 compared tislelizumab + carboplatin + paclitaxel (Arm A) vs. carboplatin + paclitaxel (Arm C) and separately tislelizumab + carboplatin + nab-paclitaxel (Arm B) vs. carboplatin + paclitaxel (Arm C). The study randomized patients 1:1:1 between the three arms. The median PFS results for tislelizumab + carboplatin + paclitaxel (Arm A) and tislelizumab + carboplatin + nab-paclitaxel (Arm B) were the same. The hazard ratios were 0.52 for Arm A vs. Arm C and 0.48 for Arm B vs. Arm C. KEYNOTE-407 randomized patients to receive either pembrolizumab or placebo plus carboplatin and either paclitaxel or nab-paclitaxel; the study was stratified by the choice of taxane.

Conference Call

Summit Therapeutics Inc. will host a conference call and live webcast to discuss recent updates related to ivonescimab, including data released at ESMO (Free ESMO Whitepaper), on Monday, October 20, 2025, at 8:00am ET. Conference call and webcast information will be accessible through our website www.smmttx.com.

An archived edition of the webcast will be available on our website later in the day on Monday.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC (Free SITC Whitepaper), 2023) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 3,000 patients have been treated with ivonescimab in clinical studies globally.

Summit began its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In early 2025, the Company began enrolling patients for HARMONi-7. Summit intends to open clinical trial sites in the United States for the Phase III HARMONi-GI3 study in colorectal cancer (CRC) by the end of 2025.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutant, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third generation EGFR tyrosine kinase inhibitor (TKI) (e.g., osimertinib). Enrollment in HARMONi was completed in the second half of 2024, and top-line results were announced in May of 2025, with detailed results provided in September 2025.

HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression.

HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

HARMONi-GI3 is a planned Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC. In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

Akeso is actively conducting multiple Phase III clinical studies in settings outside of NSCLC, including biliary tract cancer, colorectal cancer, breast cancer, pancreatic cancer, small cell lung cancer, and head and neck cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting.

(Press release, Summit Therapeutics, OCT 19, 2025, View Source [SID1234656802])

On October 19, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results from the Phase III IMvigor011 study evaluating Tecentriq (atezolizumab) as an adjuvant treatment for people with muscle-invasive bladder cancer (MIBC) who are at risk of recurrence after surgery (cystectomy) and have detectable circulating tumor DNA (ctDNA). In this ctDNA-guided setting, Tecentriq reduced the risk of death (overall survival, OS) by 41% and the risk of disease recurrence or death (disease-free survival, DFS) by 36%, both compared with placebo. This ctDNA-guided approach, using Natera’s SignateraTM ctDNA Molecular Residual Disease (MRD) test, spared people at low risk of recurrence from unnecessary treatment and side effects. The safety profile was consistent with previous studies of Tecentriq.

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These results are being presented as part of the Presidential Symposium at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025. They will also be discussed with health authorities, including the U.S. Food and Drug Administration.

"These clinically meaningful results show that Tecentriq helped people with muscle-invasive bladder cancer live longer and without their disease returning," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "The use of serial ctDNA testing to detect molecular residual disease may also advance bladder cancer treatment by combining a precision diagnostic with cancer immunotherapy."

"Even after surgery, most people with muscle-invasive bladder cancer will face the physical and emotional toll of further treatment," said Thomas Powles, lead principal investigator of IMvigor011, professor of genitourinary oncology; chair of Barts Cancer Centre at St. Bartholomew’s Hospital. "These results indicate that with Signatera ctDNA testing, we may be able to identify those at risk of recurrence who could benefit from adjuvant atezolizumab treatment and spare others from unnecessary therapy, paving the way for a more personalized treatment approach."

At median follow up of 16.1 months, median DFS was 9.9 months in the Tecentriq arm versus 4.8 months in the placebo arm (stratified hazard ratio [HR]=0.64; 95% CI: 0.47-0.87, p=0.0047). Median OS was 32.8 months in the Tecentriq arm versus 21.1 months in the placebo arm (HR=0.59; 95% CI: 0.39-0.90, p=0.0131). People who persistently tested for no detectable ctDNA had low risk of recurrence.

More than 150,000 people worldwide are diagnosed with MIBC each year. It is an aggressive type of cancer, with poor long-term outcomes and high treatment burden. Despite this, personalized treatment approaches lag behind other cancer types. ctDNA-guided treatment could change this, by helping healthcare professionals tailor treatment more precisely to improve clinical benefit and reduce unnecessary intervention.

About the IMvigor011 study
IMvigor011 [NCT04660344] is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with Tecentriq (atezolizumab) compared with placebo in participants with muscle-invasive bladder cancer (MIBC) who are circulating tumor DNA (ctDNA)-positive and are at risk of recurrence following cystectomy. IMvigor011 utilized Natera’s Signatera as the clinical trial assay. This personalized ctDNA test for the detection of MRD is currently under review by the FDA for use as a companion diagnostic. 761 people participated in the surveillance phase of IMvigor011 and those with positive Signatera tests (250 people) joined the treatment phase, where they received either Tecentriq or placebo. The primary endpoint is investigator-assessed disease-free survival (DFS). Secondary endpoints include overall survival (OS) and tolerability, amongst others.

About Tecentriq (atezolizumab)

Tecentriq (atezolizumab) is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

What is Tecentriq?

Tecentriq is a prescription medicine used to treat:

Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used alone as a treatment for your lung cancer:
to help prevent your lung cancer from coming back after your tumor(s) has been removed by surgery and you have received platinum-based chemotherapy, and
you have stage 2 to stage 3A NSCLC (talk to your healthcare provider about what these stages mean), and
your cancer tests positive for "PD-L1".
Tecentriq may be used alone as your first treatment when your lung cancer:
has spread or grown, and
your cancer tests positive for "high PD-L1", and
your tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as your first treatment when your lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC", and
your tumor does not have an abnormal "EGFR" or "ALK" gene.

Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as your first treatment when your lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC", and
your tumor does not have an abnormal "EGFR" or "ALK" gene.

Tecentriq may be used alone when your lung cancer:

(Press release, Genentech, OCT 19, 2025, View Source [SID1234656787])
has spread or grown, and
you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
If your tumor has an abnormal "EGFR" or "ALK" gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

Adults with a type of lung cancer called "extensive stage small cell lung cancer (SCLC)", which is SCLC that has spread or grown

Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment
Tecentriq may be used with the medicine lurbinectedin as maintenance treatment when your lung cancer:
has not progressed after first treatment with Tecentriq or atezolizumab and hyaluronidase-tqjs and the chemotherapy medicines carboplatin and etoposide.

Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq may be used with the medicine bevacizumab when your liver cancer:

has spread or cannot be removed by surgery, and
you have not received other medicines by mouth or injection through your vein (IV) to treat your cancer.

Adults with a type of skin cancer called melanoma. Tecentriq may be used with the medicines cobimetinib and vemurafenib when your melanoma:

has spread to other parts of the body or cannot be removed by surgery, and
has a certain type of abnormal "BRAF" gene. Your healthcare provider will perform a test to make sure this Tecentriq combination is right for you.

Adults and children 2 years of age and older with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq may be used when your sarcoma:

has spread to other parts of the body or cannot be removed by surgery.

It is not known if Tecentriq is safe and effective when used:

in children younger than 2 years of age for the treatment of ASPS.
in children for the treatment of NSCLC, SCLC, HCC or melanoma.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during your treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worse signs or symptoms, including:

Lung problems

cough
shortness of breath
chest pain
Intestinal problems

diarrhea (loose stools) or more frequent bowel movements than usual
stools that are black, tarry, sticky, or have blood or mucus
severe stomach-area (abdomen) pain or tenderness
Liver problems

yellowing of your skin or the whites of your eyes
severe nausea or vomiting
pain on the right side of your stomach area (abdomen)
dark urine (tea colored)
bleeding or bruising more easily than normal
Hormone gland problems
headaches that will not go away or unusual headaches
eye sensitivity to light
eye problems
rapid heartbeat
increased sweating
extreme tiredness
weight gain or weight loss
feeling more hungry or thirsty than usual
urinating more often than usual
hair loss
feeling cold
constipation
your voice gets deeper
dizziness or fainting
changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems

decrease in your amount of urine
blood in your urine
swelling of your ankles
loss of appetite
Skin problems

rash
itching
skin blistering or peeling
painful sores or ulcers in mouth or nose, throat, or genital area
fever or flu-like symptoms
swollen lymph nodes

Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Call or see your healthcare provider right away for any new or worse signs or symptoms, including:

Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
Persistent or severe muscle pain or weakness, muscle cramps
Low red blood cells, bruising

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

chills or shaking
itching or rash
flushing
shortness of breath or wheezing
dizziness
feeling like passing out
fever
back or neck pain

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Tecentriq. Your healthcare provider will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with Tecentriq. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Tecentriq if you have severe side effects.

Before you receive Tecentriq, tell your healthcare provider about all of your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Tecentriq can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with Tecentriq.
You should use an effective method of birth control during your treatment and for at least 5 months after the last dose of Tecentriq.
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into your breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

Feeling tired or weak
decreased appetite
nausea
cough
shortness of breath

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

feeling tired or weak
nausea
hair loss
constipation
diarrhea
decreased appetite

The most common side effects of Tecentriq when used in hepatocellular carcinoma (HCC) with bevacizumab include:

high blood pressure
feeling tired or weak
too much protein in the urine

The most common side effects of Tecentriq when used in melanoma with cobimetinib and vemurafenib include:

skin rash
joint, muscle, or bone pain
feeling tired or weak
liver injury
fever
nausea
itching
swelling of legs or arms
mouth swelling (sometimes with sores)
low thyroid hormone levels
sunburn or sun sensitivity

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of Tecentriq. Ask your healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

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 Genentech at 1-888-835-2555.

Please see full Prescribing Information and Medication Guide for additional Important Safety Information.

(Press release, Genentech, OCT 19, 2025, View Source [SID1234656787])

On October 19, 2025 Daiichi Sankyo reported initial results from the dose escalation part of the first-in-human phase 1/2 trial of DS-3939 demonstrated promising clinical activity in patients with previously treated advanced solid tumors refractory to standard treatment. These data were presented today during a proffered paper session (917O) at the 2025 European Society for Medical Oncology (#ESMO25).

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DS-3939 is a specifically engineered, potential first-in-class tumor-associated mucin-1 (TA-MUC1) directed DXd antibody drug conjugate (ADC) discovered and being developed by Daiichi Sankyo (TSE: 4568).

TA-MUC1 is a tumor-specific transmembrane glycoprotein that is overexpressed in most human epithelial cancers, making it a promising target for cancer therapy.1,2 Currently, there are no TA-MUC1 directed medicines approved for any type of cancer.

Preliminary safety and efficacy results of DS-3939 were reported from the dose escalation part of the phase 1/2 trial in 64 patients with advanced solid tumors, including 16 with non-small cell lung cancer (NSCLC), 12 with pancreatic ductal adenocarcinoma, nine with urothelial carcinoma, eight with ovarian cancer, seven with biliary tract cancer, seven with colorectal cancer and five with breast cancer.

Patients in the dose escalation phase of the study (n=64) received a median of three prior therapies (range, 1-17) for locally advanced/metastatic disease, including more than one-third receiving prior topoisomerase I inhibitor treatment (n=24; 37.5%). As of the data cut-off on August 1, 2025, 15 patients (23.4%) were still being treated with DS-3939.

The safety and tolerability of DS-3939 was evaluated at increasing dose levels from 1.0 mg/kg to 10.0 mg/kg. The most common treatment-emergent adverse events (TEAEs) of any grade in >20% of patients were nausea (60.9%), vomiting (35.9%), fatigue (28.1%), anemia (26.6%), constipation (26.6%), decreased appetite (23.4%), diarrhea (23.4%) and decreased neutrophil count (23.4%). Grade 3 or higher TEAEs occurred in 46.9% of patients (n=30) and the most common (>2%) included decreased neutrophil count (15.6%), anemia (10.9%), pneumonitis (4.7%) and decreased platelet count (3.1%). There were three dose-limited toxicities observed, including one grade 3 anemia needing transfusion (4.0 mg/kg dose), one grade 3 abdominal pain (6.0 mg/kg dose) and one grade 4 decreased platelet count (8.0 mg/kg dose). All grade adjudicated as treatment-related interstitial lung disease (ILD)/pneumonitis occurred in 10.9% (n=7) of patients. The majority of ILD events were low grade (grade 2 [n=6 or 9.4%]) with one grade 3 (n=1 or 1.6%) event as determined by an independent adjudication committee. Following the data cut-off of August 1, 2025, two ILD events were adjudicated as grade 5 and two additional ILD events are pending adjudication.

Preliminary efficacy results were reported across dose levels from 1.0 mg/kg to 10.0 mg/kg of DS-3939. One confirmed complete response was observed in a patient with ovarian cancer and 10 confirmed partial responses were seen in patients with ovarian cancer (n=5), NSCLC (n=4) and breast cancer (n=1). Thirty-nine cases of stable disease were observed in patients with NSCLC (n=11), urothelial carcinoma (n=8), pancreatic ductal adenocarcinoma (n=6), colorectal cancer (n=5), biliary tract cancer (n=4), breast cancer (n=3) and ovarian cancer (n=2) after a median follow-up of 8.8 months (range, 0.6-22.9).

"These initial results are encouraging for patients with advanced solid tumors where treatment options remain limited once standard therapies are no longer effective," said Manish R. Patel, MD, Director of Drug Development, Florida Cancer Specialists and Sarah Cannon Research Institute. "Enrollment continues into the dose expansion part of the trial to help us better understand the potential role DS-3939 may play in treating numerous types of advanced solid tumors."

"These first-in-human results offer preliminary evidence that targeting the novel tumor antigen TA-MUC1 may be a promising treatment approach for multiple types of cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Additionally, these results represent the sixth antibody drug conjugate from the pipeline of Daiichi Sankyo with encouraging early phase data further demonstrating the portability of our DXd antibody drug conjugate technology to new tumor targets."

About the Phase 1/2 Trial
The two-part, multicenter, open-label, first-in-human phase 1/2 trial is assessing the safety and efficacy of DS-3939 in patients with locally advanced, metastatic or unresectable solid tumors not amenable to standard of care treatment for each tumor type.

The first part of the trial (dose escalation) assessed the safety and tolerability of increasing doses of DS-3939 to determine the maximum tolerated dose and/or the recommended doses for expansion (RDEs) in patients with locally advanced, metastatic or unresectable solid tumors.

The second part of the trial (dose expansion) consists of multiple expansion cohorts to assess the safety and efficacy of DS-3939. The trial will evaluate safety endpoints, including dose-limiting toxicities and adverse events, and efficacy endpoints, including objective response rate, disease control rate, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetic and biomarker endpoints also will be assessed.

The trial is ongoing and enrolling patients across multiple tumor types at sites globally, including Asia, Europe and North America. For more information, please visit ClinicalTrials.gov.

About TA-MUC1
TA-MUC1, a tumor-specific transmembrane glycoprotein, is a molecular target that is expressed across a broad range of solid tumors, but has limited expression in normal human tissues.1 Based on the overexpression of TA-MUC1 in solid tumors, it is an attractive target for cancer therapy.2 Currently, there are no TA-MUC1 directed therapies approved for any type of cancer.

About DS-3939
DS-3939 is an investigational, potential first-in-class TA-MUC1 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DS-3939 is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo. DS-3939 is comprised of a humanized anti-TA-MUC1 antibody, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

(Press release, Daiichi Sankyo, OCT 19, 2025, View Source [SID1234656803])

On October 18, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the first presentation of results from the pivotal Phase 3 KEYNOTE-B96 trial, also known as ENGOT-ov65, evaluating KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with chemotherapy (paclitaxel) with or without bevacizumab for the treatment of patients with platinum-resistant recurrent ovarian cancer. These late-breaking data will be presented today during a Presidential Symposium session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Presentation #LBA3).

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At the first interim analysis, with a median study follow-up of 15.6 months, KEYTRUDA plus chemotherapy with or without bevacizumab (n=322) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), the study’s primary endpoint, reducing the risk of disease progression or death by 30% (HR=0.70 [95% CI, 0.58-0.84]; p<0.0001) in the all comers population of patients with platinum-resistant recurrent ovarian cancer compared to placebo plus chemotherapy with or without bevacizumab (n=321). The 12-month PFS rate for these patients receiving the KEYTRUDA regimen was 33.1% (95% CI, 27.7-38.5) versus 21.3% (95% CI, 16.6-26.4) for patients receiving the placebo regimen. In patients whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1), KEYTRUDA plus chemotherapy with or without bevacizumab (n=234) reduced the risk of disease progression or death by 28% (HR=0.72 [95% CI, 0.58-0.89]; p=0.0014) compared to placebo plus chemotherapy with or without bevacizumab (n=232). The 12-month PFS rate was 35.2% (95% CI, 28.8-41.7) for the KEYTRUDA regimen versus 22.6% (95% CI, 17.0-28.7) for the placebo regimen.

"There are very few treatments we can offer patients living with platinum-resistant recurrent ovarian cancer that are able to reduce the risk of disease progression or death," said Dr. Nicoletta Colombo, director of the Gynecologic Oncology Program at the European Institute of Oncology in Milan, Italy. "Results from KEYNOTE-B96 have the potential to mark a significant step forward in the treatment of platinum-resistant recurrent ovarian cancer and demonstrate that adding pembrolizumab to chemotherapy, with or without bevacizumab, could potentially be an additional effective option for these patients."

At the second interim analysis, with a median study follow-up of 26.6 months, the KEYTRUDA regimen also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), a key secondary endpoint, in patients whose tumors express PD-L1 (CPS ≥1), reducing the risk of death by 24% (HR=0.76 [95% CI, 0.61-0.94]; p=0.0053) compared to placebo plus chemotherapy with or without bevacizumab. The 12-month OS rate for patients receiving the KEYTRUDA regimen was 69.1% versus 59.3% for patients receiving the placebo regimen. Eighteen-month OS rates were 51.5% and 38.9%, respectively.

"These results build upon the success of KEYTRUDA in gynecologic cancers and support the potential use of KEYTRUDA for patients with platinum-resistant ovarian cancer," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "As the first immunotherapy with data demonstrating improved survival in certain patients with platinum-resistant recurrent ovarian cancer, this KEYTRUDA-based regimen underscores our commitment to helping to provide patients with more treatment options to meet their unique needs. These data have the potential to change the treatment paradigm for patients like these with platinum-resistant recurrent ovarian cancer."

Treatment-related adverse events (TRAEs) occurred in 97.8% of patients receiving the KEYTRUDA regimen (n=320) and 95.3% of patients receiving the placebo regimen (n=318); Grade 3-5 TRAEs occurred in 67.5% versus 55.3%, respectively. TRAEs led to death in 0.9% of patients receiving the KEYTRUDA regimen and 1.6% of patients receiving the placebo regimen. No new safety concerns were identified.

Immune-mediated adverse events (AEs) and infusion reactions of any grade occurred in 39.1% of patients receiving the KEYTRUDA regimen and 18.9% of patients receiving the placebo regimen. The most common of these events (occurring in ≥10% of patients) was hypothyroidism (17.8%) in patients receiving the KEYTRUDA regimen. Immune-mediated AEs led to death in 0.6% of patients in the KEYTRUDA arm and in no patients in the placebo arm.

Based on these data from the first and second interim analyses of the KEYNOTE-B96 trial, the U.S. Food and Drug Administration (FDA) has accepted for priority review a new supplemental Biologics License Application (sBLA) seeking approval of KEYTRUDA in combination with chemotherapy with or without bevacizumab for the treatment of patients with platinum-resistant recurrent ovarian cancer. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of Feb. 20, 2026. As previously announced, in the final analysis of the trial, KEYNOTE-B96 also met its secondary endpoint of OS for all comers. These final analysis data will be presented at an upcoming medical meeting.

KEYTRUDA is not approved to treat ovarian cancer (see selected KEYTRUDA indications in the U.S. below). LYNPARZA (olaparib), which is being jointly developed and commercialized by AstraZeneca and Merck, has three approved ovarian cancer indications in the U.S.: in first-line maintenance treatment of BRCA-mutated advanced ovarian cancer, following complete or partial response to first-line platinum-based chemotherapy; in first-line maintenance treatment of HRD-positive advanced ovarian cancer in combination with bevacizumab, following complete or partial response to first-line platinum-based chemotherapy; and in maintenance treatment of BRCA-mutated recurrent ovarian cancer, following complete or partial response to platinum-based chemotherapy. For each of these indications, patients are selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA (see indications for LYNPARZA below).

As announced, data from the REJOICE-Ovarian01 trial in collaboration with Daiichi Sankyo evaluating raludotatug deruxtecan (R-DXd) in patients with platinum-resistant, high-grade ovarian, primary peritoneal or fallopian tube cancer will be presented at the 2025 ESMO (Free ESMO Whitepaper) Congress. R-DXd was recently granted Breakthrough Therapy Designation by the U.S. FDA for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab, based in part on data from the REJOICE-Ovarian01 trial. R-DXd was discovered by Daiichi Sankyo and is being jointly developed by Daiichi Sankyo and Merck.

About KEYNOTE-B96/ENGOT-ov65
KEYNOTE-B96, also known as ENGOT-ov65, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05116189) sponsored by Merck and conducted in collaboration with the European Network for Gynecologic Oncology Trial (ENGOT) groups investigating KEYTRUDA in combination with chemotherapy (paclitaxel) with or without bevacizumab compared to placebo plus chemotherapy with or without bevacizumab for the treatment of platinum-resistant recurrent ovarian cancer. The primary endpoint is PFS, and OS is a key secondary endpoint. The trial enrolled 643 patients who were randomized to receive either KEYTRUDA (400 mg intravenously every six weeks for approximately two years) plus paclitaxel with or without bevacizumab, or placebo plus paclitaxel with or without bevacizumab.

About platinum-resistant ovarian cancer
Ovarian cancer often begins in the fallopian tubes or on the outer surface of the ovaries. It is the eighth most commonly diagnosed cancer and the eighth leading cause of cancer death among women worldwide. Globally, there were more than 324,000 patients diagnosed with ovarian cancer and almost 207,000 deaths from the disease in 2022. In many regions, its incidence has been increasing, with estimates projecting a 42% increase in new cases worldwide by 2040. In the U.S., it is estimated there will be approximately 20,890 patients diagnosed with ovarian cancer and about 12,730 deaths from the disease in 2025.

The primary aim of first-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission. Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens. Approximately 25% of these patients develop resistance within six months of completing first-line platinum-based chemotherapy, and this is defined as primary platinum-resistant ovarian cancer. Prognosis is particularly poor for these patients and treatment options are limited.

(Press release, Merck & Co, OCT 18, 2025, View Source [SID1234656770])

On October 18, 2025 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported data from the dose escalation portion of the Phase 1/2 study of JK06, a 5T4-targeted antibody drug conjugate (ADC), in patients with unresectable locally advanced or metastatic cancer, including non-small cell lung cancer (NSCLC) and breast cancer, which is being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

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Data presented at ESMO (Free ESMO Whitepaper) include 34 patients enrolled in Europe with advanced relapsed/refractory solid tumors who were treated with JK06, once every three weeks, across five dose levels (1.5-8.0 mg/kg) in dose escalation. Among the 34 patients, 29 were response-evaluable, all having failed standard of care therapy, and among whom 83% had received three or more prior lines of treatment and 59% had received four or more prior lines of therapy at the time of enrollment.

Key efficacy findings among the 29 response-evaluable patients include:

6 patients attained confirmed partial responses (PRs) (21%).
Among 13 NSCLC patients, 5 attained confirmed PRs (ORR 38%), with the longest duration of response lasting 30 weeks.
Among 7 response-evaluable breast cancer patients, 1 attained a confirmed PR with a duration of response lasting 18 weeks.
PRs were observed at 3.0 mg/kg (1 NSCLC), 4.5 mg/kg (3 NSCLC and 1 breast cancer), and 6.0 mg/kg (1 NSCLC).
Treatment with JK06 has been generally well-tolerated with predominantly low grade (Grades 1 and 2), manageable toxicities, such as fatigue, alopecia, decreased appetite, dry eye and diarrhea. Among treatment-related adverse events (TRAEs) occurring in at least 5% of patients, only the following ≥ Grade 3 events were observed:

At dose levels 1.5-3.0 mg/kg (n=12 patients), 1 patient with Grade 3 peripheral neuropathy.
At dose level 4.5 mg/kg (n=15 patients), 1 patient with Grade 3 keratitis.
At dose levels 6.0-8.0 mg/kg (n=7 patients), 1 patient with Grade 3 fatigue, 1 patient with Grade 3 ALT increase, and 1 patient with Grade 5 pneumonitis.
Pharmacokinetic analysis demonstrated free monomethyl auristatin E (MMAE) levels that were favorable at dose levels up to 4.5 mg/kg.
"We are encouraged by the promising preliminary data demonstrating the combination of safety and efficacy of JK06 among heavily pre-treated metastatic solid tumors, including in NSCLC and breast cancer, supporting our belief that JK06 has the potential to be a first-in-class, differentiated therapy for patients with 5T4-expressing cancers," said Sam Murphy, Chief Executive Officer of Salubris Biotherapeutics. "We look forward to advancing the study into dose expansion in tumor-specific cohorts for NSCLC and breast cancer, while continuing to explore activity in other solid tumors known to overexpress 5T4, as we aim to improve outcomes for these patients with advanced, aggressive disease and limited therapeutic options."

The Phase 1/2 open-label, dose-escalation and expansion study (NCT06667960) to assess the safety, pharmacokinetics, and preliminary efficacy of JK06 is ongoing, and the cohort expansion phase, which is currently enrolling, will determine the recommended Phase 2 dose for further development.

Details of the ESMO (Free ESMO Whitepaper) presentation are as follows:

Title: A Phase 1/2 Study of JK06, a 5T4-Targeted Antibody Drug Conjugate (ADC), in Patients with Unresectable Locally Advanced or Metastatic Cancer
Presenter: Nuria Kotecki, M.D. at Institut Jules Bordet, Anderlecht, Belgium
Abstract #: 961P
Session: Developmental Therapeutics
Date/Time: Sunday, October 19, 2025 | 12:00 – 1:00 PM CEST

About JK06

JK06 is a first-in-class quadrivalent, biparatopic ADC that selectively targets 5T4 with a monomethyl auristatin E (MMAE) payload. 5T4 is an oncofetal protein that is overexpressed in a wide range of solid tumors, including NSCLC, breast, renal and genitourinary cancers, and is associated with more aggressive tumor progression and reduced survival. JK06 has demonstrated picomolar affinity for 5T4 and rapid internalization due to the biparatopic design. Together with stable, site-specific payload conjugation, JK06 has further demonstrated robust efficacy and a clean safety profile in non-clinical studies.

(Press release, Salubris Biotherapeutics, OCT 18, 2025, View Source [SID1234656756])