On May 19, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that an abstract reporting on the first-in-human study of the Bcl-2 inhibitor, lisaftoclax (APG-2575), in patients with relapsed/refractory chronic lymphocytic lymphoma/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies has been published in the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting’s official website (Press release, Ascentage Pharma, MAY 19, 2021, View Source;ascentage-pharma-to-announce-updated-data-of-lisaftoclax-apg-2575-demonstrating-an-orr-of-around-80-and-therapeutic-potential-in-patients-with-rr-cllsll-in-oral-presentation-301295527.html [SID1234580321]). Results from this global Phase I study demonstrated an ORR of 85.7%, and favorable tolerability and safety profiles in patients with R/R CLL /SLL.

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The updated results from this study will be released in an oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting convening on June 4 to 8, 2021. This year, abstracts reporting on four clinical studies of the Ascentage Pharma’s three apoptosis-target drug candidates have been selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting, and two have been selected for oral presentations.

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

"As a Bcl-2 inhibitor that has demonstrated efficacy, lisaftoclax is the second in the world and the first in China. These data of lisaftoclax suggest the potential for a safe, efficacious, and ‘patient-friendly’ treatment alternative for patients with R/R CLL and other hematologic malignancies," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Moreover, these results which will be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting are a testament to our progress in advancing the research and development of apoptosis-targeted therapeutics. We will strive to further accelerate global clinical development programs of these novel therapeutics to benefit patients in China and around the world as early as possible."

Those abstracts to be presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting are as follows (two abstracts on APG-115 are simultaneously published in a separate press release):

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

Format: Oral Presentation
Abstract: #7502
Time: 11:30 – 14:30 EDT, June 7, 2021
Session Track: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Highlights:
This first-in-human global Phase I study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of lisaftoclax in patients with R/R CLL and other HMs. Lisaftoclax was orally administered once daily in a 28-day cycle. Patients with CLL or intermediate-high tumor lysis syndrome (TLS) risk were initiated on a daily ramp-up schedule until the dose assigned before the study cycles.
As of January 7, 2021, 35 patients had been enrolled and treated with lisaftoclax at doses ranging from 20 to 1,200 mg, with a median of 2 (range: 1-13) prior lines of treatment. These patients had been diagnosed with R/R CLL/SLL (n=15), multiple myeloma (MM, n=6), follicular lymphoma (FL, n=5), Waldenström macroglobulinemia (WM, n=4); and either acute myeloid leukemia (AML), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), myelodysplastic syndromes (MDS), or hairy cell leukemia (HCL) (n=1 each).
Lisaftoclax was well tolerated, with manageable adverse events (AEs). No dose-limiting toxicity (DLT) was observed even at the maximum dose of 1,200 mg. The MTD has not been reached, and no laboratory or clinical TLS has been reported. Hematologic treatment-related adverse events (TRAEs) of any grade in over 10% patients included neutropenia and anemia, while nonhematologic TRAEs included fatigue, diarrhea, and nausea.
12 of 14 evaluable patients with R/R CLL/SLL achieved partial response (PR), for an ORR of 85.7% and a median time to response of 3 treatment cycles (range: 2-7). Absolute lymphocyte counts (ALCs) were reduced at lisaftoclax doses as low as 20 mg/day.
The preliminary PK profile showed that exposures increased with lisaftoclax doses from 20 to 1,200 mg (average half-life: 4-5 hours). On BH3 profiling, lisaftoclax rapidly triggered changes in Bcl-2 complex in CLL/SLL patient samples, which were consistent with rapid clinical reductions in ALCs.
In conclusion, efficacy and safety data showed that the Bcl-2 inhibitor lisaftoclax offers a potential alternative treatment for patients with R/R CLL/SLL and other HMs, with a daily ramp-up schedule that may be more patient-friendly and a favorable preliminary safety profile.
Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

Format: Poster Presentation
Abstract: #TPS8589
Time: 09:00 EDT, June 4, 2021
Session Track: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Highlights:
This open-label, multicenter Phase Ib/II study is assessing the safety of preliminary efficacy of pelcitoclax in combination with paclitaxel in patients with R/R SCLC.
Pelcitoclax is being administered by intravenous (IV) infusion on Days 1, 8, and 15, with paclitaxel at the fixed-dose of 80 mg/m2 on Days 1 and 8 of a 21-day cycle.
The primary endpoints of the Phase Ib part of this study include MTD and RP2D. The efficacy of pelcitoclax combined with paclitaxel will be determined in the Phase II part of the study using a Simon two-stage design, with ORR as the primary endpoint. Other endpoints of the Phase II study include PK, progression-free survival, and overall survival.
This study was designed to enroll 58 patients. As of February 8, 2021, 15 patients have been enrolled.
About Lisaftoclax (APG-2575)

Lisaftoclax is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. Lisaftoclax is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China. At present, lisaftoclax has been cleared and approved to enter multiple Phase Ib/II studies in the US, China, and Australia, and is being developed globally for the treatment of multiple hematologic malignancies.

About Pelcitoclax (APG-1252)

Pelcitoclax is a novel, highly potent, small-molecule drug designed to restore apoptosis through selective inhibition of Bcl-2 and Bcl-xL proteins. Multiple Phase Ib/II studies of pelcitoclax as a single agent or in combinations for the treatment of a range of advanced tumors, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), are being conducted in China, Australia, and the US.

On May 19, 2021 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, MasterKey therapies, reported initial data from the Phase 1 dose-escalation portion of the MasterKey-01 trial of BDTX-189 in patients with advanced solid tumors harboring any one of more than 48 oncogenic alterations in the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) oncogenes (Press release, Black Diamond Therapeutics, MAY 19, 2021, View Source [SID1234580337]). These data provide early proof-of-concept for BDTX-189, including evidence of anti-cancer activity and a safety profile that is in-line with the Company’s preclinical expectations. The data announced today will be presented in poster presentations at the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 4-8, 2021.

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"These encouraging Phase 1 safety and anti-cancer activity data provide early proof-of-concept for BDTX-189 as a differentiated MasterKey inhibitor of undrugged oncogenic mutants of EGFR, including EGFR Exon 20 insertion mutations and oncogenic mutants of HER2," said Rachel Humphrey, M.D., Chief Medical Officer of Black Diamond Therapeutics. "We look forward to the continued advancement of BDTX-189 through clinical development and remain on track to initiate the potentially pivotal Phase 2 portion of the MasterKey-01 trial in the second half of 2021."

"These initial data suggest BDTX-189 may provide meaningful clinical benefit to patients with advanced solid tumors, including those with allosteric EGFR and HER2 mutations," said Alison Schram, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center. "The favorable tolerability profile demonstrated thus far supports the potential of BDTX-189 to address the unmet need in this patient population, for which there are no currently approved targeted therapies and where other in-clinic agents are limited by toxicity."

MasterKey-01 Part A Dose-Escalation Study Design

Part A is a Phase 1, first-in-human, open-label dose escalation study, comprised of initial single-patient, accelerated titration cohorts followed by multiple-patient cohorts utilizing a Bayesian Optimal Interval (BOIN) design. Part A is designed to determine the recommended Phase 2 dose and schedule for the QD and twice-daily (BID) regimens in patients with solid tumors with an allosteric HER2 or HER3 mutation; EGFR or HER2 Exon 20 insertion mutation; HER2 amplified or overexpressing tumor; or EGFR Exon 19 deletion or L858R mutation.

Initial Study Results

As of the data cut-off date of April 2, 2021, 55 patients from the QD regimen were dosed across the dosing range, 25-400 mg QD fasting (n = 12), 800 mg QD fasting (n = 21), 800 mg QD non-fasting (n = 9), 1000 mg QD fasting (n = 7), and 1200 mg QD fasting (n = 6). The dose-escalation portion successfully enrolled patients with a broad range of tumor types and genomic alterations. Tumor types enrolled included non-small cell lung cancer (NSCLC), breast, colorectal (CRC), ovary, biliary, pancreas, cervical, cancer of unknown primary, kidney, salivary, prostate, signet ring cell, liver, and bladder. Genomic alterations enrolled included HER2 amplification and the following mutations: allosteric HER2, EGFR Exon 20 insertion, HER2 Exon 20 insertion, EGFR Exon 19 del./L858R, and HER3.

PK

The PK data for the BDTX-189 QD regimen demonstrated dose-dependent increases in exposure up to 800 mg QD, achieving the predicted efficacious exposure at 800 mg QD. BDTX-189 was rapidly absorbed, with a short elimination half-life of 1.3-4.4 hours, consistent with preclinical predictions. No apparent accumulation or change in exposure at steady state was observed.

Safety

BDTX-189 demonstrated a favorable tolerability profile, with no dose-limiting toxicities at doses of ≤800 mg QD fasting and non-fasting in the dose-escalation cohorts. 800 mg non-fasting was selected as the preliminary RP2D for the QD regimen.

The most common drug-related adverse events were gastrointestinal in nature, the majority of which were low grade and generally medically manageable. At 800 mg QD fasted or non-fasted (n = 30), the most common drug-related adverse events were diarrhea (50%, 7% Gr3), nausea (50%, 7% Gr3), vomiting (30%, 3% Gr3), ALT increased (20%, 10% Gr3), AST increased (13%, 3% Gr3), fatigue (20%, 0% Gr3), skin disorders (13%, 0% Gr3), and decreased appetite (10%, 0% Gr3).

Efficacy

In a heavily pre-treated patient population, including patients who had received prior EGFR/HER2 tyrosine kinase inhibitors (TKI), evidence of anti-cancer activity was observed. Among all cancer type/genomic alteration pairs, two had ≥ three RECIST-evaluable patients dosed at ≥800 mg QD: NSCLC harboring either EGFR Exon 20 mutations (n = 3) or HER2 Exon 20 mutations (n = 3). In the separate group of patients with solid tumors harboring HER2-amplification, six patients dosed at ≥800 mg QD were evaluable by RECIST.

Three patients with NSCLC EGFR Exon 20 dosed at ≥800 mg QD (all at 800 mg QD) were evaluable by RECIST at the time of data cut-off, all of whom had received prior EGFR/HER2-targeted therapy. One confirmed partial response was observed in a patient who had previously responded and then progressed on poziotinib (at the data cut-off, 53% tumor regression observed and treatment with BDTX-189 ongoing 13+ weeks). One patient with stable disease and one patient with progressive disease were observed.
Three patients with NSCLC HER2 Exon 20 dosed at ≥800 mg QD (all at 800 mg QD) were evaluable by RECIST at the time of data cut-off, two of whom had received prior EGFR/HER2-targeted therapy. All three patients demonstrated stable disease.
Six patients with HER2-amplification across a range of tumor types dosed at ≥800 mg QD were evaluable by RECIST at the time of data cut-off, two-thirds of whom had received prior EGFR/HER2-targeted therapy. One confirmed partial response (cancer of unknown primary; at data cut-off, 90% tumor reduction and treatment with BDTX-189 ongoing 24+ weeks), one unconfirmed partial response (NSCLC), two patients with stable disease (ovarian and pancreatic), and two patients with progressive disease were observed.
"We’re incredibly encouraged by the rapid progress of the MasterKey-01 study and promising proof-of-concept data for BDTX-189. These preliminary data support the differentiated profile of BDTX-189 as a MasterKey inhibitor of diverse oncogenic alterations in EGFR and HER2, as well as initial validation of Black Diamond’s proprietary MAP drug discovery engine and MasterKey approach to drug development," said David M. Epstein, President and Chief Executive Officer of Black Diamond Therapeutics. "We’d like to thank all the patients, their families, and their caregivers for participating in this study."

Black Diamond is continuing to dose patients in the ongoing QD dose-escalation portion and the food effect cohort, as well as enrolling and dosing patients in the BID dose-escalation portion. The Company will initiate the safety expansion cohort ahead of the Phase 2 portion of the MasterKey-01 study, which remains on track for initiation in the second half of 2021.

Part B is a Phase 2, open-label, multi-center study designed to determine anti-cancer activity and safety in adult patients with solid tumors harboring an allosteric HER2 mutation or EGFR or HER2 Exon 20 insertion mutation. This portion of the trial will enroll patients in focused tumor/mutation cohorts and is designed to be potentially pivotal. Additionally, based on early proof-of-concept data, Black Diamond is exploring the potential for further clinical development in the HER2-amplified setting.

The data announced today will be presented in poster presentations at the upcoming ASCO (Free ASCO Whitepaper) meeting:

Title: Safety and Preliminary Efficacy from the Phase 1 Portion of MasterKey-01: A First-in-Human Dose-Escalation Study to Determine the Recommended Phase 2 Dose (RP2D), Pharmacokinetics (PK), and Preliminary Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB mutations, in Patients with Advanced Solid Malignancies
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 9:00 AM ET
Abstract ID: 3086

Title: Clinical pharmacokinetics of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 9:00 AM ET
Abstract ID: 3097

Conference Call and Webcast:

In connection with today’s announcement, Black Diamond’s management team will host a conference call and live audio webcast at 6:00 PM ET today, Wednesday, May 19, 2021.

The live audio webcast and accompanying slides may be accessed through the Events page in the Investors section of the Company’s website at www.blackdiamondtherapeutics.com. Alternatively, the conference call may be accessed as follows:

For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors section of the Company’s website.

About BDTX-189

BDTX-189 is an orally available, irreversible, and ATP competitive small molecule inhibitor that is designed to block the function of a family of oncogenic epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) proteins across a range of tumor types. BDTX-189 is designed as a MasterKey inhibitor targeting a family of previously undrugged and functionally similar oncogenic mutations in a tumor-agnostic manner. These mutations include extracellular domain allosteric mutations of HER2, as well as EGFR and HER2 kinase domain Exon 20 insertions, and additional activating oncogenic drivers of EGFR and HER2. BDTX-189 is also designed to spare normal, or wild-type, EGFR, which we believe has the potential to improve upon the toxicity profiles of current EGFR/HER2 kinase inhibitors. Currently, there are no medicines approved by the U.S. Food and Drug Administration (FDA) to target all of these oncogenic mutations with a single therapy.

BDTX-189 is currently being evaluated in a Phase 1/2 clinical trial (MasterKey-01) in adult patients with advanced solid tumors expressing a range of alterations of EGFR and HER2 receptors, including oncogenic MasterKey mutations, HER2-WT amplification, HER3 mutation, EGFR Exon 19 deletion, and L858R mutation who have no standard therapy available or for whom standard therapy is considered unsuitable or intolerable. In July 2020, the FDA granted Fast Track designation to BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric HER2 mutation or an EGFR or HER2 Exon 20 insertion mutation who have progressed following prior treatment and who have no satisfactory treatment options.

On May 19, 2021 NexImmune, Inc. (Nasdaq: NEXI), a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to orchestrate a targeted immune response by directing the function of antigen-specific T cells, reported that clinical data from its Phase 1/2 dose escalation study of NEXI-001 will be presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting being held virtually from June 4 – June 8, 2021 (Press release, NexImmune, MAY 19, 2021, View Source [SID1234580370]).

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Poster Presentation:

Title: Preliminary Analysis of a Phase 1/2 Study of NEXI-001 Donor-Derived Multi-Antigen-Specific CD8+ T Cell Treatment of Relapsed Acute Myeloid Leukemia (AML) After Allogeneic Hematopoietic Cell Transplantation (HCT)

Abstract #: 2538

Session Title: Poster Session: Developmental Therapeutics – Immunotherapy

Authors: Monzr M. Al Malki, MD1, Sumithira Vasu, MBBS2, Dipenkumar Modi, MD3, Miguel-Angel Perales, MD4, Megan Nelson, RN, BSN5, Donna Bui1, Vineetha Edavana, PhD6, Sojung Kim, PhD6, Lauren Suarez, PhD6, Mathias Oelke, PhD6, Robert D. Knight, MD6, and Juan C. Varela, MD, PhD5

(1) Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA, (2)Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, (3)Division of Oncology, Karmanos Cancer Center/ Wayne State University, Detroit, MI, (4)Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, (5)Advent Health Blood and Marrow Transplant Program, Orlando, FL, (6)NexImmune Inc, Gaithersburg, MD.

On May 19, 2021 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease through the inhibition of SEMA4D, reported that Dr. Maurice Zauderer, chief executive officer, will deliver a company presentation at the 2021 Jefferies Virtual Healthcare Conference, which is being held June 1-4, 2021 (Press release, Vaccinex, MAY 19, 2021, View Source [SID1234580420]). Dr. Zauderer will present updates on Vaccinex’s neurology programs in Huntington’s and Alzheimer’s disease and its collaboration with Merck (Keynote B84) for combination immunotherapy in Head & Neck Squamous Cell Carcinoma with Vaccinex’s pepinemab antibody and Merck’s KEYTRUDA. Management will be available during the conference for virtual one-on-one meetings.

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Presentation details:
Date: Tuesday, June 1
Time: 4:30pm ET

Following the presentation, a live video webcast may be accessed through the "Events" page of the Vaccinex website, www.vaccinex.com.

On May 19, 2021 Dana-Farber Cancer Institute researchers reported that they are presenting dozens of research studies at the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Dana-Farber Cancer Institute, MAY 19, 2021, View Source [SID1234580471]). The studies will be presented during the virtual program on June 4-8, 2021. ASCO (Free ASCO Whitepaper) is the world’s largest clinical cancer research meeting, attracting more than 30,000 oncology professionals from around the world.

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Toni K. Choueiri, MD, the director of the Lank Center for Genitourinary Oncology at Dana-Farber, will present results from the randomized, double-blind, phase III KEYNOTE-564 trial evaluating pembrolizumab versus placebo after surgery in patients with renal cell carcinoma (abstract LBA5) during ASCO (Free ASCO Whitepaper)’s Plenary Session on Sunday, June 6, 2021, 1:00pm-4:00pm ET. The plenary session features five studies deemed to have the greatest potential impact on patient care.

F. Stephen Hodi, MD, the director of the Melanoma Center and Center for Immuno-Oncology at Dana-Farber is co-senior author on the RELATIVITY-047 study evaluating combination treatment with two immunotherapies (relatlimab plus nivolumab) versus nivolumab alone in first-line treatment for patients with advanced melanoma (abstract 9503). Findings from the RELATIVITY-047 study will be presented during the Melanoma/Skin Cancers Oral Abstract Session on Sunday, June 6, 2021, 8:00am-11:00am ET. The study is included in the ASCO (Free ASCO Whitepaper) Press Program.

Other key research shows new treatments and diagnostic advances in lung cancer, leukemia, head and neck cancer, pediatrics, and many others. Some of the research highlights include:

Antibody drug conjugate shows promise against non-small cell lung cancer resistant to targeted therapy

An antibody fused to a targeted drug has produced impressive results in a Phase I clinical trial involving patients with advanced non-small cell lung cancer (NSCLC) whose tumors had become resistant to a standard targeted therapy. Dana-Farber’s Pasi A. Jänne, MD, PhD, is lead author of the study.

The trial evaluated the safety and effectiveness of patritumab deruxtecan, an antibody drug conjugate consisting of an antibody targeting the protein HER3 and an inhibitor of the topoisomerase 1 enzyme, in 57 patients whose NSCLC carried an EGFR gene mutation but no longer responded to EGFR-targeting drugs. Patients who become resistant to such drugs and to platinum-based chemotherapy usually have few treatment options.

After a median treatment time of 5.5 months, 39% of the participants had a confirmed clinical response to the conjugate – a reduction in tumor size or extent. Among these patients, the median progression-free survival was 8.2 months. The antitumor effect occurred in patients whose resistance to EGFR inhibitors arose from a range of molecular mechanisms and in those with no clear identifiable resistance mechanism.

The most common severe side effects were decreased blood platelet counts, lowered counts of neutrophils (a type of white blood cell), and fatigue – all consistent with previous safety studies.

The results have prompted investigators to open a Phase 2 trial of the conjugate for patients with EGFR-mutant NSCLC whose disease has become resistant to EGFR-targeting drugs and chemotherapy.

Title: Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC)

Abstract: 9007

Presenter: Pasi A. Jänne, MD, PhD

Session/Time: Oral Abstract Session: Lung Cancer – Non-Small Cell Metastatic; Broadcasting: June 4, 1:00pm-4:00pm

PET scans following initial treatment help many patients with bulky early-stage Hodgkin lymphoma avoid radiotherapy

Many early-stage patients with bulky classic Hodgkin lymphoma (cHL) can avoid radiotherapy treatment and still have excellent outcomes, according to a clinical study in which treatment was adapted to findings on PET imaging. Bulky disease – characterized by large tumors typically in the center of the chest – is associated with poorer outcomes in cHL and is traditionally treated with radiotherapy following chemotherapy. However, radiation treatment to the chest can have long-term toxic effects including an increased risk of breast cancer and heart problems.

The results, presented by Ann LaCasce, MD, MMSc, of Dana-Farber, included 94 patients with stage IA-IIB cHL and disease bulk greater than 10 cm or .33 maximum intrathoracic diameter on chest X-ray. Patients received two cycles of chemotherapy (ABVD) and then underwent PET imaging. Patients whose disease showed uptake less than liver on interim PET scan (PET2-) – 78% of the patients — received four additional cycles of chemotherapy, but no radiotherapy. Patients classed as PET2+ received intensified chemotherapy with four cycles of escBEACOPP plus radiation therapy.

The estimated progression-free survival (PFS) was 93.1% in the PET2- patients and 89.7% in PET2+ patients. With a median follow-up of 5.5 years, estimated 3-year overall survival was 98.6% in PET2- patients and 94.4% in PET2+ patients. (Overall survival was not a primary or secondary outcome of the study).

The investigators said the PET-adapted approach achieved excellent PFS outcomes "that allowed omission of radiotherapy in 78 percent of patients." The PET2+ patients who received BEACOPP and radiotherapy "did not have inferior outcomes."

Title: CALGB 50801 (Alliance): PET adapted therapy in bulky stage I/II classic Hodgkin lymphoma (cHL)

Abstract: 7507

Presenter: Ann S. LaCasce, MD, MMSc

Session/Time: Oral Abstract Session: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia; Broadcasting: June 7, 11:30am-2:30pm

Additional cycle of pembrolizumab before surgery improves response rates in locally advanced head and neck cancer

Increasing neoadjuvant pembrolizumab from one to two cycles prior to surgery improved pathological response rates in patients with surgically resectable locally advanced, HPV-negative head and neck squamous cell carcinoma, reported Ravindra Uppaluri, MD, PhD, Dana-Farber/Brigham and Women’s Cancer Center. A previous study in which patients (36 total) received one neoadjuvant cycle of pembrolizumab followed by surgery two to three weeks later yielded a 22% rate of >50% pathologic response (tumor cell death and other evidence of response designated as pTR-2) and a 22% pTR-1 rate (10-49% pathologic response). The new report was on a 28-patient phase 2 trial in which patients received two cycles of pembrolizumab 42 and 21 days prior to surgery. Twelve of 28 patients (43%) experienced a pTR-2 and four (16%) of these patients had a major pathologic response including 1 complete response at the primary site.

Neoadjuvant therapy was well tolerated and clinical outcomes in this advanced disease population were excellent with only one recurrence noted to date. The researchers said the data suggest that the frequency of pathologic responses to neoadjuvant pembrolizumab can be improved by increasing the number of cycles and the treatment interval.

Title: Enhanced pathologic tumor response with two cycles of neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC)

Abstract: 6008

Presenter: Ravindra Uppaluri, MD, PhD

Session/Time: Oral Abstract Session: Head and Neck Cancer; Broadcasting: June 7, 2:45pm-5:45pm

Molecular profiling of tumor tissue can benefit many young patients with cancer, study suggests

Testing solid tumors for genetic changes that can be targeted by drugs has revolutionized the treatment of many adults with cancer. New research by scientists at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center suggests it can have significant benefits for many younger patients as well.

Alanna J. Church, MD, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, will present results from the GAIN/iCat2 consortium study, which is evaluating the use of genomic profiling of solid tumors in children and young adults. The report includes data on 345 study participants with molecular profiling, who were diagnosed with solid, non-brain tumors at age 30 or younger. 299 patients (87%) had at least one genomic alteration that could impact the diagnosis, treatment, and prognosis of their disease, the researchers found.

Thirty-one patients were treated with matched targeted therapies and six patients had extraordinary responses to treatment. All patients with extraordinary responses matched to a gene fusion, and 78% of diagnostically significant alterations were fusions.

Molecular tumor profiling has a significant impact on diagnosis and treatment recommendations for young patients with solid tumors. These results emphasize the importance of fusion detection for patients with sarcomas and rare tumors,said Church, the lead author of the study, which was the highest rated pediatric oncology abstract at the ASCO (Free ASCO Whitepaper) conference, and winner of the Conquer Cancer Nachman Award.

Title: Clinical impact of molecular tumor profiling in pediatric, adolescent, and young adult patients with extra-cranial solid malignancies: An interim report from the GAIN/iCat2 study

Abstract: 10005

Presenter: Alanna J. Church, MD

Session Time: Oral Abstract Session: Pediatric Oncology I; Broadcasting: June 5, 10:00am-1:00pm

A full list of Dana-Farber Oral Presentations at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting is available here.

Additionally, Dana-Farber researchers are recipients of ASCO (Free ASCO Whitepaper)’s Special Awards, the Society’s highest honors.

Jennifer A. Ligibel, MD, director of the Leonard P. Zakim Center for Integrative Therapies and Healthy Living and the director of the Center for Faculty Well-Being at Dana-Farber, is the recipient of the Hologic, Inc Endowed Women Who Conquer Cancer Mentorship Award.

Tracy A. Balboni, MD, MPH, FAAHPM, radiation oncologist at Dana-Farber/Brigham and Women’s Cancer Center and a professor of radiation oncology at Harvard Medical School, is the recipient of the Walther Cancer Foundation Palliative and Supportive Care in Oncology Endowed Award. Her award lecture is available for on-demand viewing during the ASCO (Free ASCO Whitepaper) conference, starting June 4, 2021, 9:00am ET.

Read more about this year’s Dana-Farber ASCO (Free ASCO Whitepaper) Special Awards here.