On September 17, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported updated efficacy and safety results from the TAMARACK Phase 2 study of vobramitamab duocarmazine (vobra duo), an antibody-drug conjugate (ADC) that targets B7-H3, for patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, MacroGenics, SEP 16, 2024, View Source [SID1234646659]). The data were featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain from September 13-17, 2024.

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"A key reason for conducting the TAMARACK study was to test the hypothesis that we could improve upon the duration of vobra duo treatment observed in the Phase 1 study by reducing the starting dose from 3.0 mg/kg to either 2.0 or 2.7 mg/kg and increasing the dosing interval from every three weeks to every four weeks. In doing so, our aim was to improve safety and tolerability, extend the treatment duration and achieve improved rPFS as compared to the result in our Phase 1 mCRPC dose expansion cohort," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We believe that these latest results from TAMARACK continue to demonstrate that vobra duo is an active drug in prostate cancer. Ultimately, our path forward for the molecule will depend on the final safety and efficacy data, including mature median rPFS, which we expect to have in hand no later than early 2025. We expect to make decisions about potential future development in the context of a competitive treatment landscape assessment, resource allocation across our clinical portfolio and potential partnering opportunities for vobra duo."

TAMARACK Study Demographics

The abstract submitted to ESMO (Free ESMO Whitepaper) was based on a data cut-off as of April 12, 2024; updated data based on a cut-off date of July 9, 2024, are included below and are reported in the Company’s poster presentation at ESMO (Free ESMO Whitepaper).
The TAMARACK trial enrolled a total of 181 participants, with 176 participants receiving at least one dose of vobra duo at either 2.0 mg/kg q4W (n=90) or 2.7 mg/kg q4W (n=86). As of the data cut-off date, 23 and 16 participants remained on treatment in the 2.0 mg/kg and 2.7 mg/kg cohorts, respectively. While mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression, and survival.
Baseline Characteristics:
•Enrolled study participants had a median age of 70 years (range, 35-89).
•88 Study participants (48.6%) had an ECOG performance status of 1 or 2.
•30 Study participants (16.6%) had visceral disease at baseline, with liver or lung disease in 25 participants (13.8%).
•81 Study participants (44.8%) had measurable disease at baseline, and 97 (53.6%) had received prior taxane.
•Both treatment arms were well-balanced across most baseline characteristics, including prior use of taxanes, androgen receptor axis-targeted (ARAT) treatment, poly-ADP ribose polymerase (PARP) treatment, and baseline PSA.
TAMARACK Efficacy Results as of July 9, 2024 Cut-off Date
Overall, the Company believes that the results to date from the TAMARACK study indicate antitumor activity associated with vobra duo in mCRPC as demonstrated by the protocol-specified primary endpoint of landmark 6-month radiographic progression-free survival (rPFS) rate, as well as other measures of tumor response.
•In the intent-to-treat (ITT) population, 6-month rPFS rate was 69% for the 2.0 mg/kg arm (95% CI, 57-79) and 70% for the 2.7 mg/kg arm (95% CI, 58-79).
•Landmark 6-month rPFS rates were consistent across taxane-naïve study participants (ranging from 66-82%) and taxane pre-treated study participants (ranging from 60-73%), regardless of treatment arm.

•Although immature, with only 65 PFS events (35.9%) as of the data cut-off, median rPFS was approximately 8.5 months for the 2.0 mg/kg cohort (95% CI, 7.2-11.2) and 7.5 months for the 2.7 mg/kg cohort (95% CI, 7.2-10.6). Because these results were immature as of the cutoff date, they are likely to change as additional events accrue.
Tumor response rates
•Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg arm, the confirmed objective response rate (ORR) was 20.0% (n=9) and the unconfirmed ORR was 26.7% (n=12).
•Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg arm, the confirmed ORR was 40.6% (n=13) and the unconfirmed ORR was 46.9% (n=15).
•Confirmed ORR was comparable between taxane-naïve study participants (26.7%, n=12/45) and taxane pre-treated study participants (17.5%, n=11/63), regardless of treatment arm.
•Tumor responses did not appear to correlate with baseline B7-H3 expression based on archival tissue samples of mixed age.
TAMARACK Safety Results as of July 9, 2024 Cut-off Date
Overall summary of adverse events (AEs)
•In the 2.0 mg/kg cohort, 65.6% of study participants (n=59) experienced a Grade ≥3 treatment-emergent AE (TEAE); this cohort had a discontinuation rate of 25.6% (n=23) and a dose reduction rate of 50.0% (n=45) due to TEAEs.
•In the 2.7 mg/kg cohort, 62.8% of study participants (n=54) experienced a Grade ≥3 TEAE; this cohort had a discontinuation rate of 38.4% (n=33) and a dose reduction rate of 54.7% (n=47) due to TEAEs.
•The most common (occurring in ≥20% of study participants) all-grade TEAEs were: asthenia, edema peripheral, decreased appetite, nausea, pleural effusion, diarrhea, fatigue, constipation, anemia, palmar-plantar erythrodysesthesia (PPE, or hand-foot syndrome), neutropenia, and stomatitis. The majority of TEAEs with a ≥10% incidence rate in either treatment arm was limited to Grade 1/2 events.
•Rates of pleural effusion, pericardial effusion, and PPE for both the 2.0 mg/kg cohort (28.8%, 13.3%, 18.9%, respectively) and the 2.7 mg/kg cohort (44.2%, 17.5%, 28%, respectively) decreased compared to the Phase 1 mCRPC dose expansion cohort (48.8%, 17.1%, 46.3%, respectively), despite an increased median number of doses of vobra duo administered on TAMARACK.

•Eight fatal treatment-related AEs as assessed by the treating physician: five in the 2.0 mg/kg cohort and three in the 2.7mg/kg cohort. These include three events of pneumonitis, and one event each of cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage.
•Rates of treatment-related AEs (including all grades and Grade ≥3) and treatment-related severe AEs were similar between taxane-naïve and taxane pre-treated study participants.

Tolerability findings

•In the 2.0 mg/kg cohort, 25.6% of study participants (n=23) remained on study drug as of July 9, 2024. Study participants received a median number of 6 doses (range, 1-11), with a median dose intensity (calculated as a percentage of the total planned dose that was administered) of 92.6% (range, 64.2-106.1%).
•In the 2.7 mg/kg cohort, 18.6% of study participants (n=16) remained on study drug as of the data cut-off date. Study participants received a median number of 6 doses (range, 1-12), with a median dose intensity of 81.7% (range, 40.5-104.3%).
•Taxane-naïve study participants experienced higher rates of dose reductions due to TEAEs (62.7%) and dose interruptions due to TEAEs (70.7%) compared to taxane pre-treated study participants (44.6% and 43.6%, respectively).

ESMO Poster Presentation

Title: TAMARACK: Randomized Phase 2 trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)
Presenter / Lead Author: Johann de Bono, M.D., M.Sc., Ph.D., FRCP, FMedSci, Division of Clinical Studies, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK
Presentation ID: 1654P
Session Date: Sunday, September 15, 2024
Poster Display Time: 9:00 a.m. – 5:00 p.m. CEST
The poster presentation is available for download under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source

Conference Call

The Company will host a conference call to discuss the TAMARACK poster data and provide a general corporate update on Monday, September 16, 2024, at 8:00am ET. The call will be led by Scott Koenig, M.D., Ph.D., President and Chief Executive Officer; Stephen Eck, M.D., Ph.D., Senior Vice President – Chief Medical Officer; and Jim Karrels, Senior Vice President – Chief Financial Officer.

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

About Vobra Duo and the TAMARACK Study

Vobra duo is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation. The TAMARACK Phase 2 study of vobra duo is being conducted in participants with mCRPC who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks (q4W).

On September 16, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported updated data, including median progression-free survival (mPFS) and overall survival (OS) findings, from the Phase 2 trial of zanidatamab, an investigational dual HER2-targeted bispecific antibody, in combination with chemotherapy as first-line treatment for patients with HER2-expressing advanced or metastatic gastroesophageal adenocarcinoma (mGEA) (Press release, Jazz Pharmaceuticals, SEP 16, 2024, View Source [SID1234646675]).

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Data from 41 patients with HER2-positive mGEA who were treated with zanidatamab in combination with physician’s choice of chemotherapy treatment demonstrated a mPFS of 15.2 [95% CI: 9.5, 33.4] months. After a median duration of follow-up of 41.5 (range, 23.0-52.7) months, the median OS was not mature, a Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] and the 30-month overall survival was 59% [95% CI: 41.0, 73.0].

"Gastroesophageal adenocarcinoma (GEA) represents one of the most common tumor types worldwide; however, developing effective treatment options for GEA patients has been challenging," said Dr. Elena Elimova, lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre, Toronto, Canada. "Despite recent advancements for patients, the sustained clinical antitumor activity seen in this trial demonstrates the potential for zanidatamab to address a significant unmet patient need in HER2-positive GEA."

"The updated results from this Phase 2 trial reaffirm zanidatamab’s potential as a foundational treatment for patients with HER2-positive mGEA and showcase the promise of this HER2-targeted bispecific antibody to treat HER2-expressing cancers," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "We look forward to continuing to advance our broader clinical development program for zanidatamab in GEA, including the Phase 3 first-line clinical trial HERIZON-GEA-01 that is expected to read out in the second quarter of 2025, and other HER2-expressing solid tumors, with the goal of supporting more patients with HER2-positive cancers."

Phase 2 mGEA Trial Results
The data include efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with HER2-expressing mGEA, which comprises gastric, esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with HER2-expressing mGEA (41 patients with HER2-positive mGEA) were enrolled from 15 sites across the United States, Canada and South Korea, and patients were administered zanidatamab with physician’s choice of chemotherapy treatment. Currently, chemotherapy-based regimens are the standard first-line combination therapy for 1L mGEA.

The longer-term data (median duration of follow-up of 41.5 [range, 23.0-52.7] months) demonstrates the promising antitumor activity of zanidamatab combined with chemotherapy as a first-line therapy for HER2-positive mGEA.

Treatment with zanidatamab resulted in a cORR of 84% [95% CI: 68.0, 94.0], an increase of 5% from the cORR previously reported, and one additional patient achieved a complete response for a total of four patients achieving complete response among 37-response evaluable patients.
The median duration of response was 18.7 months [95% CI: 8.3-NE] with 10 patients having an ongoing response at the time of data cutoff.
The mPFS was 15.2 [95% CI: 9.5, 33.4] months.
The Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] with a 30-month overall survival of 59% [95% CI: 41.0, 73.0].
With additional follow-up, the safety and tolerability profile of zanidatamab plus chemotherapy remained manageable with no new safety signals identified. Diarrhea was the most common Grade 3-4 treatment-related adverse events (TRAEs) (35%); the incidence of Grade 3-4 diarrhea was <15% for patients treated after the implementation of mandated antidiarrheal prophylaxis. Treatment discontinuation due to TRAEs were infrequent, and there were no treatment-related deaths.

These data were presented in a poster session entitled Zanidatamab + Chemotherapy for First-Line Treatment for HER2+ Advanced or Metastatic Gastroesophageal Adenocarcinoma (mGEA) during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting taking place in Barcelona, Spain. The presentation is available to conference registrants on the ESMO (Free ESMO Whitepaper) conference website (Presentation Number 1423P).

Jazz continues to enroll patients in the Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing mGEA. This is an events-based trial; top-line data from this trial is expected to read out in the second quarter of 2025.

Phase 2 Colorectal Cancer (CRC) Trial Results Presented as Mini-Oral at ESMO (Free ESMO Whitepaper) 2024
In addition to the mGEA trial presentation, a mini-oral was also presented at ESMO (Free ESMO Whitepaper) 2024 from another arm of the same Phase 2, open-label trial (NCT03929666) that includes a cohort of patients with metastatic CRC treated with first-line zanidatamab plus chemotherapy ± bevacizumab (bev). In 11 response-evaluable patients, there were 10 confirmed partial responses and 1 patient with stable disease as a best response. The cORR was 91% (95% CI: 58.7, 99.8) and median duration of response was not reached (2.9+,16.7+ months). All patients experienced TRAEs – Grade 3-4 TRAEs occurred in five (38%) patients, three (23%) of whom experienced diarrhea. No patients discontinued zanidatamab due to a TRAE and there were no treatment-related deaths. Zanidatamab plus chemotherapy ± bev demonstrated encouraging antitumor activity with a generally manageable safety profile as first-line treatment for patients with HER2-positive mCRC.

About Zanidatamab
Zanidatamab is an investigational dual HER2-targeted bispecific antibody that simultaneously binds to two distinct sites on HER2, known as biparatopic binding. This unique design and enhanced binding results in multiple mechanisms of action, including HER2 and HER3 signal blockade, removal of HER2 protein from the cell surface and enhanced immune effector functions, such as complement-dependent cytotoxicity (CDC), which leads to encouraging antitumor activity. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review of the Biologics License Application (BLA) for zanidatamab with a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024. Zanidatamab was also granted Breakthrough Therapy designation in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC) and given two Fast Track designations: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide, and approximately 20% of patients have HER2–positive disease.1,2,3 HER2–positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options.

On September 16, 2024 Personalis, Inc. (Nasdaq: PSNL), a leader in MRD testing, reported findings presented this week at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain (Press release, Personalis, SEP 16, 2024, View Source [SID1234646691]). Personalis’ NeXT Personal assay was designed to detect and monitor residual and recurrent disease (MRD) in cancer patients by detecting very small traces of circulating tumor DNA (ctDNA) in the blood. It was launched to the clinic in late 2023 and is being co-commercialized in partnership with Tempus AI, Inc.

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Two studies were presented at ESMO (Free ESMO Whitepaper) further demonstrating the importance of using ultrasensitive MRD assay to monitor lung cancer patients and patients on immunotherapy.

In the first of these studies, Professor Charles Swanton and his colleagues at Cancer Research UK, University College London and the Francis Crick Institute analyzed over 400 non-small cell lung cancer (NSCLC) patients from their TRACERx lung cancer study, using the NeXT Personal assay. It represents one of the largest and most comprehensive MRD studies in lung cancer performed to date. These new results expand on and further strengthen the ground-breaking results of the initial study presented at last year’s ESMO (Free ESMO Whitepaper) congress.

Strong detection rates for residual lung cancer in the landmark period, the first 120 days after surgery
A high percentage of these landmark detections (42%) occur in the ultrasensitive range (less than 80 ppm) enabled by NeXT Personal
Pre-operative detections predict clinical outcome in lung adenocarcinoma, the most common type of lung cancer
Dynamic monitoring with NeXT Personal through adjuvant therapy can stratify patients for clinical outcome
NeXT Personal demonstrated high sensitivity for detecting early-stage lung cancer recurrence with detection months ahead of imaging and the ability to identify low and high-recurrence risk patients before and after surgery.

In the second abstract, Dr. Rodrigo Toledo at the Vall d’Hebron Institute of Oncology (VHIO) presented data on a large cohort of over 200 late-stage cancer patients on immunotherapy profiled using the NeXT Personal assay, significantly expanding on the initial cohort first presented earlier this year. The study was unique in having a validation set of patients and it demonstrated that patients who had a significant decrease in ctDNA levels in response to immunotherapy had significantly longer overall survival than those who did not.

"The expanded data from the TRACERx and VHIO studies are important for demonstrating the robust performance and clinical importance of our NeXT Personal MRD test," said Richard Chen, Chief Medical Officer and EVP of R&D at Personalis. "There are now 6 studies that have been presented pointing to a critical role of an ultra-sensitive MRD approach for identifying patients at risk for cancer recurrence, monitoring therapy response, and detecting cancer recurrence earlier."

On September 16, 2024 Alligator Bioscience AB ("Alligator") (Nasdaq Stockholm: ATORX) and Aptevo
Therapeutics ("Aptevo") (Nasdaq: APVO) reported positive interim data from the dose escalation phase of their Phase 1 trial evaluating ALG.APV-527 for the treatment of solid tumors likely to express the tumor antigen 5T4 (Press release, Alligator Bioscience, SEP 16, 2024, View Source [SID1234646643]). The results, which include clinical activity, safety, tolerability outcomes, pharmacokinetics and pharmacodynamics were presented in a poster session on Saturday, September 14, 2024, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress in Barcelona, Spain.

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ALG.APV-527 is a first-in-class bispecific antibody that targets 4-1BB and the tumor antigen 5T4. The compound is being evaluated in a multi-center, dose escalation trial that has 18 patients included in the safety analysis. These patients received multiple prior rounds of therapy for the treatment of solid tumor types. The trial is approaching full enrollment and interim results include:

Clinical Activity/Efficacy

Nine of 15 efficacy evaluable patients (60%) have a best overall response to date of stable disease (SD)
The longest SD duration was in a breast cancer patient who entered the study with progressive disease, achieved stable disease and remained on study for >11 months. This patient successfully transitioned to a higher dose level twice
One colon cancer patient with sustained SD remains on study for more than four months
Safety and Tolerability

ALG.APV-527 demonstrated positive safety and tolerability across all cohorts
A maximum tolerated dose has not been identified
Evidence of favorable pharmacokinetics and biological activity of ALG.APV-527

ALG.APV-527 could be measured in all patients with serum concentration of ALG.APV-527 consistent with the administered dose and preclinical predictions.
Biomarker analyses confirm biological activity of ALG.APV-527
"4-1BB has been a target of interest—though with excess toxicity—for decades, and novel bispecific approaches like this will enable us to maximize anti-tumor immunity while limiting the systemic toxicity concerns that have plagued this key immune costimulatory receptor. With this backdrop, these Phase 1 interim results are very encouraging, with ALG.APV-527 showing a positive safety profile with 60% of evaluable patients achieving stable disease, meaning not progressing for variable time frames including one breast cancer patient being treated with monotherapy on study with SD for more than 11 months. We are excited to see signs of clinical activity, underscoring the potential of the drug to benefit patients with solid tumors in the clinical setting, supported by a positive safety and tolerability profile," stated Thomas Marron, MD, PhD, Professor in Immunology & Immunotherapy and in Medicine, Hematology and Medical Oncology at Icahn School of Medicine at Mount Sinai, participating Investigator of the trial.
Trial Overview
The ALG.APV-527 Phase 1 trial is a multi-center, multi-cohort, open-label dose-escalation trial that includes administration of ALG.APV-527 in up to six escalating dose levels in a 3+3 design*. The trial is enrolling adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks. The trial is assessing the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527.

*The 3+3 design proceeds in cohorts of three patients treated at increasing dose levels. Dose escalation stops when at least two out of three or six patients experience dose limiting toxicities (DLTs) at that dose level.

About ALG.APV-527
ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. 5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer.

Preclinical studies, highlighting the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in preclinical models, has been published in the peer-reviewed publication, Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

On September 14, 2024 NuCana plc (NASDAQ: NCNA) reported final data from the Phase 2 NuTide:701 study at the ESMO (Free ESMO Whitepaper) Congress on NUC-7738 in combination with pembrolizumab for patients with metastatic melanoma who were refractory to or had relapsed on prior PD-1 inhibitor therapy (Press release, Nucana, SEP 16, 2024, View Source [SID1234646660]).

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In this cohort of 12 patients, most of whom had received at least two prior lines of PD-1 inhibitor therapy, nine (75%) achieved disease control, including two patients who achieved Partial Responses. One of these patients, who had received two prior lines of PD-1 inhibitor-based therapy and had progressed on their latest treatment of ipilimumab plus nivolumab within two months, achieved a 55% reduction in tumor volume. Seven of the 12 patients had a progression free survival time of greater than five months, which is highly atypical in this patient population. In addition to achieving these encouraging efficacy signals, the combination of NUC-7738 and pembrolizumab had a favorable safety profile.

NUC-7738’s ability to sensitize PD-1 resistant tumors to rechallenge with PD-1 inhibitors is believed to be due to its ability to target multiple aspects of the tumor microenvironment (TME) via the disruption of RNA polyadenylation and subsequent changes to gene expression in cancer cells. In support of this hypothesis, data presented from tumor biopsies obtained before and after NUC-7738 based treatment demonstrated increases in genes related to antigen presentation and T-cell activation.

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We are very excited to share these data on NUC-7738 in combination with pembrolizumab in PD-1 inhibitor refractory and resistant patients with melanoma. Outcomes in this patient population are very poor, with median progression free survival of 2-3 months with the current standard of care, so we are very encouraged that the majority of patients who received this combination achieved a progression free survival of more than five months."

Mr. Griffith continued: "The translational data that has been generated in this study and in previous non-clinical studies give us confidence that the effects we are seeing are a result of NUC-7738 making previously resistant tumors sensitive to rechallenge with PD-1 inhibitors by targeting multiple aspects of the tumor microenvironment. Our data on NUC-7738 obtained in other tumor types indicate that this phenomenon is not restricted to melanoma and that NUC-7738 may have the ability to sensitize other PD-1 inhibitor resistant tumor types. We look forward to sharing our development plans for NUC-7738 in the near future."