On May 29, 2020 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported updated data from the ongoing Phase 1 study evaluating single agent vorasidenib in isocitrate dehydrogenase (IDH)-mutant advanced solid tumors, including glioma (Press release, Agios Pharmaceuticals, MAY 29, 2020, View Source [SID1234558671]). Data from the non-enhancing glioma population were featured in an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which is being held virtually. Vorasidenib, an investigational, oral, selective, brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent Grade 2 non-enhancing glioma.

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"For patients with IDH-mutant non-enhancing glioma who currently have limited treatment options beyond chemotherapy and radiation, targeted oral options such as vorasidenib are urgently needed," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the Phase 1 dose-escalation study. "The updated results of this study in non-enhancing glioma patients provide further evidence of the potential benefit of vorasidenib for these patients, with a favorable safety profile and encouraging preliminary activity, including prolonged disease control, objective tumor responses, and clinically meaningful progression-free survival rates."

"These promising efficacy and safety data in patients with IDH-mutant non-enhancing glioma provide further support for our registration-enabling Phase 3 INDIGO study," said Chris Bowden, M.D., chief medical officer at Agios. "With vorasidenib – the first and only brain-penetrant IDH inhibitor in Phase 3 trials for low-grade glioma – we have an opportunity to target a highly prevalent driver mutation early in the disease evolution, providing a therapeutic alternative to ‘watch and wait’ that can potentially delay the need for chemotherapy and radiation."

Vorasidenib Phase 1 Dose-Escalation Study

Vorasidenib is being evaluated as a single agent in an ongoing Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid tumors (n=93), including glioma (n=52). Enrollment was completed in June 2017. As of the March 3, 2020 data cut-off, study design, enrollment and baseline characteristics of the 22 non-enhancing glioma patients are reported below:

Seventy-seven percent of patients (n=17) had World Health Organization (WHO) classified Grade 2 tumors and 23% (n=5) had Grade 3 tumors.
Ninety-one percent of patients (n=20) had an IDH1 mutation and 5% (n=1) had an IDH2 mutation. One patient did not have a biopsy but was confirmed as IDH mutant positive due to 2-HG elevation by magnetic resonance spectroscopy (MRS).
The median age of these patients is 47 years (ranging from 16 to 73).
Sixty-four percent of patients (n=14) had received prior systemic therapy. Patients had received a median of two prior systemic therapies (ranging from 1 to 4).
Fifty-nine percent of patients (n=13) had previously received temozolomide and 36% (n=8) of patients received prior radiation therapy.
Patients received daily doses of vorasidenib ranging from 10 mg to 200 mg.
Thirty-six percent of patients (n=8) remain on treatment.
Safety Data

The safety analysis conducted on the 22 patients with non-enhancing glioma as of the data cut-off demonstrated that vorasidenib has a favorable safety profile at dose levels below 100 mg once daily. Safety data for this population are consistent with the results reported for all patients enrolled in this trial at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting.

The majority of adverse events (AEs) reported by investigators were mild to moderate, with the most common (>40%) across all grades being increased alanine aminotransferase (ALT) (64%), increased aspartate aminotransferase (AST) (59%), nausea (46%) and headache (41%).
Grade 3 or higher AEs were observed in 27% of patients (n=6) with the most common being increased ALT (9%) and AST (9%).
AEs of Grade 2 or higher elevated transaminases occurred in seven non-enhancing glioma patients at the higher dose levels (≥100 mg) and resolved to Grade ≤1 with dose modification or discontinuation.
No AEs of Grade 2 or higher elevated transaminases were observed in patients at the lower dose levels (<100 mg).
Of the 14 (64%) patients who discontinued treatment, 9% (n=2) discontinued due to an AE.
Efficacy Data

Efficacy data from the 22 non-enhancing glioma patients as of the data cut-off showed:

The investigator-reported objective response rate (ORR) was 18% with one patient exhibiting a partial response and three patients exhibiting minor responses using the Response Assessment in Neuro-Oncology for low-grade glioma (RANO-LGG) criteria.
Seventy-three percent of patients (n=16) achieved stable disease according to the investigator as assessed by RANO-LGG.
With 59% of events reported, median progression free survival (PFS) was 31.4 months (95% CI 11.2, 40.8).
Twenty-four month PFS rate was 55.4%.
The median treatment duration was 25.8 months (ranging from 1.0 to 47.9) with 68% (n=15) remaining on treatment for ≥1 year.
Ongoing Phase 3 INDIGO Trials in Progress Poster
A trials in progress poster was presented at the 2020 ASCO (Free ASCO Whitepaper) Annual Meeting to highlight the ongoing global, randomized, placebo-controlled Phase 3 INDIGO study of vorasidenib in approximately 366 patients with residual or recurrent, non-enhancing, Grade 2 low-grade glioma with an IDH1 or IDH2 mutation and who have undergone surgery as their only treatment. The goal of the study is to evaluate the efficacy of vorasidenib compared with placebo based on radiographic PFS and determine whether vorasidenib could provide a therapeutic alternative to "watch and wait" to help control low-grade glioma and potentially delay the need for chemotherapy and/or radiation. The study is currently enrolling. More information can be found on the INDIGO study website.

Vorasidenib is not approved in any country for the treatment of patients with low-grade glioma.

About Glioma
Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low-grade glioma) to rapidly progressing (high-grade glioma-Glioblastoma Multiforme). Tumor enhancement is an imaging characteristic assessed by magnetic resonance imaging (MRI), and enhancing tumors are more likely to be high-grade.

Common symptoms of glioma include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor, and regardless of treatment, the majority of patients with low-grade gliomas will have recurrent disease that will progress over time. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80 percent have an IDH mutation.

On May 29, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents designed to activate immune response to cancers and infections, reported the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO2020) Virtual Scientific Program on AGEN1181 by Dr. Steven J. O’Day, the Executive Director of the John Wayne Cancer Institute and Cancer Clinic and Director of Providence Los Angeles Regional Research (Press release, Agenus, MAY 29, 2020, View Source [SID1234558670]).

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AGEN1181 is a multifunctional Fc-engineered next generation anti-CTLA-4 antibody specifically designed to improve the safety and efficacy of first-generation CTLA-4 antibodies. AGEN1181 is advancing in the clinic both as monotherapy and in combination with balstilimab (Agenus’s anti-PD-1). Patients receiving this multifunctional antibody have progressed on prior treatments including other I-O agents, such as anti-PD-1.

"I am very pleased to report data on AGEN1181 alone and in combination with balstilimab (anti-PD-1). Preliminary efficacy is encouraging with objective responses (both complete and partial) as well as prolonged stable disease in a variety of advanced cancers progressing after standard therapies," said Dr. Steven O’Day, Executive Director of the John Wayne Cancer Institute and Cancer Clinic. "Importantly, unlike first-generation CTLA-4 antibodies, we have seen no evidence of complement mediated toxicities, such as hypophysitis, with AGEN1181. These early data, including responses in patients with CD16 polymorphisms, support the accelerated development of AGEN1181 into multiple tumors, including PD-1 refractory melanoma, NSCLC, and others."

Abstract:

TPS3157

Title:

AGEN1181, A Clinical Stage Fc-engineered anti-CTLA-4 Antibody with Improved Therapeutic Potential for the Treatment of Patients with Advanced Malignancies

Presenter:

Dr. Steven J. O’Day

Session:

Developmental Therapeutics—Immunotherapy

Date/Time:

May 29, 2020; 8:00-11:00AM

Conference call scheduled on June 2, 2020

B.Riley FBR Senior Analyst Mayank Mamtani, will host a conference call for investors on Tuesday, June 2, 2020 with Dr. Steven O’Day and Dr. Charles Drake, Co-Director of the Cancer Immunotherapy Program and Co-Leader of the Tumor Biology & Microenvironment Program at Columbia University, and Jennifer Buell, PhD and President and COO of Agenus, to discuss the data coming out of the ASCO (Free ASCO Whitepaper)2020 Virtual Scientific Program.

Date: Tuesday, June 2, 2020
Time: 5:30 PM ET
Dial-in details: Investor access: 800.267.2845/973.413.6102 (Passcode: 842069)

The presentation will be available for on-demand viewing online at View Source

On May 29, 2020 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, presented updated data from its ADP-A2M4 Phase 1 trial at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Adaptimmune, MAY 29, 2020, View Source [SID1234558669]). The data demonstrate durability and responses in synovial sarcoma, supporting SPEARHEAD-1 as a potential registrational trial. The ASCO (Free ASCO Whitepaper) presentation also describes a new response in a patient with lung cancer, and a response in a patient with head and neck cancer (reported in January).

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The Company also announced new responses in the SURPASS trial, confirming the potential for SPEAR T-cell therapies targeting MAGE-A4 to treat a broad range of cancers in addition to sarcoma. These data further support the rationale for two new Phase 2 trials – SPEARHEAD-2 in head and neck cancer, which will begin later this year, and a second trial in esophagogastric junction (EGJ) cancer planned for 1H 2021. A webcast of Dr. Elliot Norry, Adaptimmune’s Chief Medical Officer, and Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer, summarizing these and other clinical data is available here: https://bit.ly/3enqBBy.

"I am pleased to announce that we have identified a new indication to progress into late stage development. We plan to initiate a Phase 2 trial in esophagogastric junction cancer in the first half of 2021, with our next-generation ADP-A2M4CD8 SPEAR T-cells. In addition, the ASCO (Free ASCO Whitepaper) data demonstrate promising durability for ADP-A2M4 in sarcoma bolstering our ambition to have our first marketed therapy in 2022," said Adrian Rawcliffe, CEO. "I’m thrilled with the responses in a broad range of tumors with our programs targeting MAGE-A4 and AFP. I am confident that we will be able to identify more indications for late stage development as more patients are treated in our trials."

During an oral presentation at ASCO (Free ASCO Whitepaper), Dr. David Hong of the MD Anderson Cancer Center reported positive durability and efficacy data in synovial sarcoma from the ADP-A2M4 Phase 1 trial. Based on these data, the Company believes that SPEARHEAD-1 can support registration for ADP-A2M4. These positive data also supported removal of the futility analysis from SPEARHEAD-1, reducing the sample size from 60 to 45 patients.

Outside of sarcoma, Dr. Hong shared a new RECIST response in a patient with lung cancer, as well as the response in a patient with head and neck cancer reported earlier this year. Further, he reported evidence of anti-tumor activity in ovarian cancer, bladder cancer, and melanoma.

In the SURPASS trial, three patients have responded out of the first four treated with ADP-A2M4CD8. One patient with EGJ cancer treated in the first dose cohort had a confirmed partial response (PR) reported in January, which remains ongoing approximately six months post-infusion. As reported today, a second patient in the first dose cohort, also with EGJ cancer, has an unconfirmed PR. The third response in the trial is an unconfirmed PR in a patient with head and neck cancer. Data from this trial will be updated and presented in the second half of 2020 at a medical conference. Based on these data, the Company plans to initiate a Phase 2 trial in EGJ cancer in the first half of 2021.

In January, the Company reported one confirmed PR in a patient with liver cancer from the ADP-A2AFP Phase 1 trial. Subsequently, this PR has been assessed as a confirmed complete response, which remained ongoing at the last assessment (Week 24). The next two patients with liver cancer (or hepatocellular carcinoma [HCC]) treated in Cohort 3 did not respond. A separate cohort for AFP expressing tumors other than HCC was initiated and the one patient treated to date has not responded. Detailed data will be presented in a poster and an oral presentation at the International Liver Congress (ILC) in August 2020 (rescheduled from April of this year).

RECIST Responses with SPEAR T-cell Monotherapy in Patients with Late Stage Cancers*

a: n=number of patients treated; b: includes one unconfirmed PR; c: patient treated in radiation sub-study of ADP-A2M4 Phase 1 trial; d: previously assessed as PR

CR=complete response; EGJ=esophagogastric junction; HCC=hepatocellular carcinoma; PR=partial response

* As of May 2020

ADP-A2M4 clinical update

·ASCO: Oral presentation by Dr. David Hong titled: "Phase 1 Dose Escalation and Expansion Trial to Assess Safety and Efficacy of ADP-A2M4 in Advanced Solid Tumors"

oSynovial sarcoma data

§50% response rate with inclusion of unconfirmed PR assessed after data cut-off (44% response rate without inclusion of unconfirmed PR)

§Median duration of response ~28 weeks, progression free survival ~20 weeks, median overall survival not reached

§3 out of the 7 responders have continued to benefit as of their one year assessments

§Disease control rate of 90% defined by best overall response (BOR) of PR or stable disease (SD) at time of data cut off (April 6, 2020)

oOther cancer indications

§Confirmed responses in lung cancer (reported today) and head & neck cancer (as reported in January)

§Of note, there was a response in a patient with rectal mucosal melanoma from the radiation sub-study of this trial (still recruiting) reported in January, which remains ongoing at Week 24. This patient was not part of the ASCO (Free ASCO Whitepaper) dataset

oMost adverse events were consistent with those typically experienced by cancer patients undergoing lymphodepletion cytotoxic chemotherapy, and cellular therapy

oTrial closed for enrollment with the exception of ongoing recruitment in the low-radiation sub-study

·SPEARHEAD-1

oIntended to be a registrational trial

oBased on the strength of the ADP-A2M4 Phase 1 data, futility analysis removed reducing the sample size from 60 to 45 patients

oRecruiting patients in 20 centers in Canada, France, Spain, and the US

oScreened more than half the patients likely required to complete the trial

oCurrently, there are more than 30 patients identified who would be eligible based on HLA and MAGE-A4 expression

oAim to complete SPEARHEAD-1 recruitment by 1H 2021 and launch in the US in 2022

Other trials in the MAGE-A4 program

SURPASS

·Out of the first 4 patients treated (2 with EGJ cancer; 1 with ovarian cancer, 1 with head and neck cancer) 3 have been assessed as PRs (1 confirmed)

o2 patients with EGJ cancer (1 confirmed PR announced in January and a second unconfirmed PR announced today)

o1 patient with head and neck cancer with an unconfirmed PR

·Based on the responses in EGJ cancer, the Company plans to initiate a new Phase 2 trial in this indication

oPlanning to present the full trial design in 2H 2020 and to initiate the trial in 1H 2021

·Enrollment in the SURPASS trial will focus on indications for which there have been early signs of efficacy, including responses, with SPEAR T-cells targeting MAGE-A4. These indications include lung, EGJ, head & neck, and bladder cancers

·Cohorts 2 and 3 were merged and 3 patients will be treated in this new group with up to 5 billion SPEAR T-cells, before moving into the expansion phase (subject to safety)

·Data will be presented at an upcoming medical oncology congress in 2H 2020

SPEARHEAD-2

·The trial will enroll 10 patients with head and neck cancer combining ADP-A2M4 with pembrolizumab following initiation of first line pembrolizumab in the relapsed/metastatic setting

·This will be the first time that a SPEAR T-cell will be used in sequence with first line systemic therapy

·All patients will be apheresed and have their cells manufactured with the intent of having their SPEAR T-cells available by the time of their first assessment on pembrolizumab

·Patients who do not respond to pembrolizumab (published response rate ~20%) or who progress after an initial response will receive SPEAR T-cells and continue to receive pembrolizumab

·All clinical sites are in the process of being initiated

ADP-A2AFP clinical trial

·There is one confirmed complete response, reported in January as a PR, in a patient with liver cancer – the first patient treated at target dose in Cohort 3

·The next two patients in this cohort did not respond

·Following requests from investigators, the Company opened a cohort for patients with non-hepatocellular carcinoma tumors that express AFP and the one patient treated in this cohort has also not responded

·Data will be presented at the International Liver Congress in August

On May 29, 2020 Trillium Therapeutics Inc. ("Trillium" or the "Company") (NASDAQ/TSX:TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported data from an ongoing phase 1 dose escalation study of TTI-622 in patients with advanced relapsed or refractory lymphoma (Press release, Trillium Therapeutics, MAY 29, 2020, View Source [SID1234558668]). The data are being presented today at a poster session at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program. TTI-622 is an innate immune checkpoint inhibitor targeting CD47, a "do not eat me" signal that cancer cells use to evade destruction by the immune system.

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"The data emerging from this dose escalation study suggest that TTI-622 is a promising and highly differentiated CD47 blocker," said Jan Skvarka, President and Chief Executive Officer of Trillium. "We are seeing strong tolerability, consistent with the red blood cell-sparing property associated with this molecule. Both drug exposure and target engagement have shown dose response relationships. Notably, in addition to the previously reported monotherapy complete response, we have observed a partial response in a second DLBCL patient."

The poster (#94, abstract #3030), entitled "Ongoing, First-in-human, Phase 1 Dose Escalation Study of the Investigational CD47-blocker TTI-622 in Patients with Advanced Relapsed or Refractory Lymphoma", will be presented by lead author Krish Patel, MD, Director of the Lymphoma Program at the Swedish Cancer Institute in Seattle. It will be available on the meeting website beginning at 8 a.m. ET on Friday, May 29 in the Developmental Therapeutics – Immunotherapy session. A copy of the poster will also be available on the Events and Presentations page of Trillium’s website.

Highlights from the Phase I Study Update

The presentation reports on data from 19 relapsed/refractory lymphoma patients who were enrolled in the first 5 cohorts, and were treated with TTI-622 monotherapy at a dose of up to 4 mg/kg.
Weekly intravenous infusions of TTI-622 were shown to be well tolerated, with no dose-limiting toxicities or drug-related grade ≥3 anemia or thrombocytopenia.
Preliminary data indicate dose-dependent increases in both drug exposure and target engagement, with receptor occupancy levels above 60% at doses of 2 mg/kg measured immediately after and 24 hours after infusion administration.
Objective responses were observed in two heavily pretreated diffuse large B-cell lymphoma (DLBCL) patients. One patient achieved a partial response (PR) at week 8 and a complete response (CR) at week 36; a second patient achieved a PR at week 8. Both patients have been continuing on study for 340 and 90 days, respectively, as of April 24, 2020.
Further dose escalation is in progress. The study is currently dosing at 8 mg/kg.
About the TTI-622 Phase I Study

This trial (NCT03530683) is a two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma. The objective of the study is to characterize safety, tolerability and pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b study, patients will be treated with TTI-622 in combination with other agents.

About TTI-622

TTI-622 is Trillium’s second SIRPαFc decoy receptor in clinical trials. It consists of the CD47-binding domain of human SIRPα linked to an IgG4 Fc region. It is designed to enhance phagocytosis and anti-tumor activity by preventing CD47 from delivering its inhibitory signal. Importantly, preclinical data indicate that TTI-622 does not bind appreciably to human red blood cells, providing a key differentiation feature.

On May 29, 2020 Novartis reported updated results from the landmark COMBI-AD clinical trial, demonstrating that treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) following the surgical removal of melanoma offers a long-term and durable relapse-free survival (RFS) benefit to high-risk patients diagnosed with stage III, BRAF-mutation positive melanoma1 (Press release, Novartis, MAY 29, 2020, View Source [SID1234558667]). Researchers reported that 52% (95% CI, 48%-58%) of patients treated with adjuvant Tafinlar + Mekinist were alive and relapse-free at five years1. Among patients in the study’s placebo arm 36% (95% CI, 32%-41%) were alive and relapse-free at the time of this analysis, generally consistent with typical melanoma relapse-free survival rates seen among patients with resected stage III disease without treatment1,3-5. Consistent RFS benefit was observed across all AJCC 7 stage III subgroups1,6.

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Median RFS, or the length of time when 50% of patients are still alive and relapse-free, was not yet reached at the 5-year data cut-off for patients on Tafinlar + Mekinist treatment, suggesting long-term benefit of targeted therapy in the adjuvant (post-surgical) setting (NR; 95% CI, 47.9 mo-NR)1. Median RFS was 16.6 months for patients taking a placebo (95% CI, 12.7-22.1 mo)1. Treatment with Tafinlar + Mekinist reduced the risk of relapse or death by 49% compared to placebo (hazard ratio [HR] 0.51; 95% CI 0.42, 0.61)1.

"Our goal as clinicians is to give our stage III patients the best chance for relapse-free survival," said Prof. Axel Hauschild, MD, Professor of Dermatology, University Hospital Schleswig-Holstein, Germany. "Results from COMBI-AD show that adjuvant treatment with Tafinlar + Mekinist after surgical resection gives melanoma patients the chance for long-term relapse-free survival. Five years is a clinically and emotionally significant milestone for patients. Recurrent BRAF+ melanoma, once spread to other organs, can be more dangerous and difficult to treat. The durable, long-term results seen among patients in the COMBI-AD trial clearly point to the important role targeted therapy plays in the adjuvant setting."

The COMBI-AD study results are drawn from a prospective analysis of 870 patients with BRAF V600-mutated melanoma treated with Tafinlar + Mekinist after their surgery1. This study represents the largest collection of data and longest follow-up to date in this patient population treated with targeted therapy2. The findings were presented at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program (Abstract #10001)1.

"The five-year survival mark is an important and predictive milestone for people with melanoma and the doctors who care for them," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "We see an almost 50% risk reduction in melanoma relapse or death in the COMBI-AD data announced today, and we believe patients will find this information helpful in choosing a treatment after surgery. We thank the patients and their families who participated in this long-term clinical trial. Their participation and commitment is helping the community learn how a BRAF-targeted therapy can reimagine outcomes for patients with resectable stage III melanoma."

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program data presentations (for registered participants).

About the COMBI-AD Study1,2,6,7
COMBI-AD is a pivotaI Phase III study evaluating Tafinlar (dabrafenib) + Mekinist (trametinib) among patients with stage III, BRAF V600E/K-mutant melanoma without prior anticancer therapy. It is the longest follow-up, at 60 months, and largest dataset to date of patients with Stage III melanoma receiving targeted therapy for adjuvant treatment.

It is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma were screened for eligibility. Subjects were randomized to receive either dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) combination therapy or two placebos for up to one year. The primary end point is recurrence-free survival, and secondary endpoints include overall survival, distant metastasis-free survival, freedom from relapse analysis and safety.

Melanoma staging assessed based on AJCC guidelines version 7.

During the five-year follow-up, updated safety analyses were not performed because no patients remained on therapy during the extended follow‐up period.

About Melanoma
There are more than 285,000 new diagnoses of melanoma (Stages 0-IV) worldwide each year, approximately half of which have a BRAF mutation8,9. Genetic tests can determine whether a tumor has a BRAF mutation10.

One way melanoma is staged is by how far it has metastasized11. In stage III melanoma, tumors have spread to the regional lymph nodes, presenting a higher risk of recurrence or metastases11. Patients who receive surgical treatment for stage III melanoma may have a high risk of recurrence because melanoma cells may remain in the body after surgery12. Generally the majority of relapses in stage III melanoma occur within 5 years13. Patients should ask their doctor if they are at risk for melanoma returning12.

About Tafinlar + Mekinist Combination
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

That has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
That has a certain type of abnormal "BRAF" (V600E or V600K mutation-positive) gene
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal "BRAF" gene from coming back after the cancer has been removed by surgery.

TAFINLAR and MEKINIST are prescription medications that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal "BRAF V600E" gene.

TAFINLAR and MEKINIST are prescription medications that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

that has spread to other parts of the body and you have no satisfactory treatment options and
that has a certain type of abnormal "BRAF" gene
TAFINLAR, in combination with MEKINIST, should not be used to treat people with wild-type BRAF melanoma. MEKINIST should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that TAFINLAR and MEKINIST, in combination, are right for you.

It is not known if TAFINLAR and MEKINIST are safe and effective in children.

TAFINLAR and MEKINIST, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When TAFINLAR is used in combination with MEKINIST, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like "coffee grounds," or red or black stools that look like tar.

MEKINIST, alone or in combination with TAFINLAR, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider immediately if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

TAFINLAR, in combination with MEKINIST, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of TAFINLAR and MEKINIST can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

TAFINLAR, in combination with MEKINIST, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

TAFINLAR, in combination with MEKINIST, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with TAFINLAR in combination with MEKINIST, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of TAFINLAR in combination with MEKINIST. In some cases these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with TAFINLAR in combination with MEKINIST. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.

TAFINLAR may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

TAFINLAR, in combination with MEKINIST, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with TAFINLAR and MEKINIST and for at least 4 months after the last dose of TAFINLAR and MEKINIST. For women of reproductive potential, TAFINLAR and MEKINIST, in combination, may harm your unborn baby. Use effective birth control (contraception) during treatment with TAFINLAR and MEKINIST in combination, and for 4 months after stopping treatment with TAFINLAR and MEKINIST. The most common side effects for patients with metastatic melanoma are: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma receiving the combination as adjuvant therapy are: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.