On May 19, 2021 AstraZeneca reported that it will present new data underscoring its ambition to redefine cancer care at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, 4 to 8 June 2021 (Press release, AstraZeneca, MAY 19, 2021, View Source [SID1234580250]).

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More than 100 abstracts will feature 21 approved and potential new medicines across the Company’s industry-leading oncology portfolio, with four abstracts selected as late-breakers, 12 oral presentations and one plenary presentation.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "Our data at ASCO (Free ASCO Whitepaper) this year show our unwavering resolve to revolutionise cancer care and strengthen our leading portfolio in lung and breast cancers as well as haematology. New results for Lynparza and Imfinzi continue to validate our strategy of treating cancer early in settings with curative intent, and data for Calquence deliver on our commitment to improve the patient experience by demonstrating efficacy with safe, tolerable medicines."

Cristian Massacesi, Senior Vice President, Head of late-stage development, Oncology R&D said: "Over the past few years, the outlook for breast cancer patients with BRCA mutations has radically changed, and the OlympiA data at ASCO (Free ASCO Whitepaper) will represent another critical step forward. We have an opportunity to fundamentally change the prognosis for women with high-risk early disease and usher in a potential new standard of care in the adjuvant setting. Additionally, promising data in triple-negative breast cancer will challenge current treatment expectations and bring hope for new approaches in this aggressive form of the disease."

Redefining survival by treating cancer earlier
A plenary presentation of results from the OlympiA Phase III trial in early breast cancer will highlight the impact of Lynparza (olaparib) on the risk of disease recurrence versus placebo in the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Lynparza is the first PARP inhibitor to demonstrate clinical benefit as an adjuvant treatment in early breast cancer. In February 2021, the trial’s Independent Data Monitoring Committee recommended moving to early primary analysis based on a planned interim analysis showing a sustainable and clinically relevant treatment effect in the primary endpoint of invasive disease-free survival.

Five-year overall survival data from the PACIFIC Phase III trial will continue to support the unprecedented and sustained survival benefits of Imfinzi (durvalumab) for patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who have not progressed following concurrent chemoradiation therapy. These data represent the longest-ever survival reported in a Phase III trial of immunotherapy in this treatment setting.

Additionally, an oral presentation of Phase II data from the externally sponsored GeparNuevo trial conducted by the German Breast Group will show initial potential of Imfinzi to improve outcomes in patients with early triple-negative breast cancer (TNBC) when added to standard neoadjuvant chemotherapy.

Transforming the patient experience
Four-year follow-up data from the ELEVATE-TN trial will confirm the sustained clinical benefit of either Calquence monotherapy or Calquence in combination with obinutuzumab, providing flexibility to tailor treatment for adults with treatment-naïve chronic lymphocytic leukaemia (CLL).

In addition, an oral presentation of detailed results from the ELEVATE-RR Phase III trial will demonstrate significantly lower atrial fibrillation, fewer cardiac events and fewer discontinuations with Calquence (acalabrutinib) versus ibrutinib in adults with previously treated CLL at high risk for progression. ELEVATE-RR is the first head-to-head Phase III trial of two Bruton’s tyrosine kinase inhibitors in CLL, confirming the favourable benefit-risk profile of Calquence for patients with CLL.

Updated data from DESTINY-Gastric01 and DESTINY-CRC01 will further support the potential role of Enhertu (trastuzumab deruxtecan) across HER2-targetable cancers. Additionally, data from a subgroup analysis of previously treated HER2-positive breast cancer patients with brain metastases in the DESTINY-Breast01 trial will reinforce the commitment to understanding the potential benefit of Enhertu in hard-to-treat patient populations.

Initial results will be shared from the BEGONIA Phase Ib/II trial testing Imfinzi combinations in metastatic TNBC, including with Enhertu. Also, data will be shared from a Phase II trial with ceralasertib, an ataxia telangiectasia and rad3-related (ATR) kinase inhibitor, in combination with Imfinzi showing that this combination demonstrated promising anti-tumour activity in melanoma patients for whom prior anti-PD1 treatment had failed.

Additional evidence will underscore the need for improved central nervous system control and the role of next-generation tyrosine kinase inhibitors (TKIs) such as Tagrisso (osimertinib) in the treatment of advanced epidermal growth factor (EGFR)-mutated NSCLC, as shown in the REFLECT retrospective real-world analysis of first- and second-generation TKIs.

Advancing an industry-leading clinical development programme
In all, AstraZeneca will share 18 posters at ASCO (Free ASCO Whitepaper) describing trials-in-progress exploring novel medicines and combinations across multiple types and stages of cancer. These posters include:

Datopotamab deruxtecan (Dato-DXd) – the TROPION-Lung01 Phase III trial testing datopotamab deruxtecan in patients with previously treated metastatic NSCLC, and the BEGONIA trial testing Imfinzi in combination with datopotamab deruxtecan in metastatic TNBC
Enhertu – trials testing Enhertu alone or in various combinations, including: DESTINY-Breast07, DESTINY-PanTumor01, and DESTINY-CRC02
Imfinzi – the MATTERHORN Phase III trial of neoadjuvant-adjuvant Imfinzi and chemotherapy in resectable gastric and gastroesophageal junction cancer, and the BEGONIA Phase I/II trial testing Imfinzi in novel combinations for 1st-line treatment of patients with TNBC, including with Enhertu and datopotamab deruxtecan.
Calquence – the ESCALADE Phase III trial of Calquence in combination with standard chemotherapy for patients age 65 and younger newly diagnosed with diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma
Camizestrant (AZD9833) – the SERENA-4 Phase III trial comparing camizestrant, a next-generation oral selective oestrogen receptor degrader (SERD), plus palbociclib, versus anastrozole plus palbociclib, in patients with oestrogen receptor-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease
Adavosertib – the ADAGIO Phase II multicentre trial of the WEE1 inhibitor adavosertib as a treatment for recurrent or persistent uterine serous carcinoma, a highly aggressive form of endometrial cancer
Collaboration in the scientific community is critical to improving outcomes for patients. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. in the US and Canada). AstraZeneca is collaborating with Daiichi Sankyo Company, Limited (Daiichi Sankyo) to develop and commercialise Enhertu and datopotamab deruxtecan globally.

Key AstraZeneca presentations during the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting1

Lead author

Abstract title

Presentation details2

Immuno-Oncology

Spigel, D

Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: An update from the PACIFIC trial.

Abstract #8511

Poster Discussion Session

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

4 June 2021

Janjigian, Y

MATTERHORN: Efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer—A randomized, double-blind, placebo-controlled, phase 3 study.

Abstract #TPS4151

Poster Session

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

4 June 2021

McCoon, P

T-cell receptor pharmacodynamics associated with survival and response to tremelimumab (T) in combination with durvalumab (D) in patients (pts) with unresectable hepatocellular carcinoma (uHCC).

Abstract #4087

Poster Session

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

4 June 2021

Schmid, P

BEGONIA: Phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC)—Initial results from arm 1, d+paclitaxel (P), and arm 6, d+trastuzumab deruxtecan (T-DXd).

Abstract #1023

Poster Discussion Session

Breast Cancer—Metastatic

4 June 2021

Schmid, P

BEGONIA: Phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first line metastatic triple-negative breast cancer (mTNBC): Addition of Arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062).

Abstract #TPS1105

Poster Session

Breast Cancer—Metastatic

4 June 2021

Kwon, M

Phase II study of ceralasertib (AZD6738), in combination with durvalumab in patients with metastatic melanoma who have failed prior anti-PD-1 therapy.

Abstract #9514

Poster Discussion Session

Melanoma/Skin Cancers

4 June 2021

Suárez, C

Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer.

Abstract #4511

Poster Discussion Session

Genitourinary Cancer—Kidney and Bladder

4 June 2021

Tumour drivers and resistance

Janzic, U

Real-world outcomes and clinical characteristics of patients with brain metastases from EGFR mutated non-small cell lung cancer: Data from a large retrospective study (REFLECT).

Abstract #9086

Poster Session

Lung Cancer—Non-Small Cell Metastatic

4 June 2021

Im, S-A

SERENA-4: A phase 3 comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease.

Abstract #TPS1101

Poster Session

Breast Cancer—Metastatic

4 June 2021

Tada, H

Adjuvant gefitinib versus cisplatin/vinorelbine in Japanese patients with completely resected, EGFR-mutated, stage II-III non-small cell lung cancer (IMPACT, WJOG6410L): A randomized phase 3 trial.

Abstract #8501

Oral Abstract Session

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

6 June 2021

Antibody drug conjugates

Yoh, K

A randomized, phase 3 study of datopotamab deruxtecan (Dato-DXd; DS-1062) versus docetaxel in previously treated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (TROPION-Lung01).

Abstract #TPS9127

Poster Session

Lung Cancer – Non-small Cell Metastatic

4 June 2021

Andre, F

Trastuzumab deruxtecan (T-DXd) combinations in patients with HER2-positive advanced or metastatic breast cancer: A phase 1b/2, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast07).

Abstract #TPS1096

Poster Session

Breast Cancer—Metastatic

4 June 2021

Li, BT

A phase 2, multicenter, open-label study evaluating trastuzumab deruxtecan (T-DXd) for the treatment of solid tumors harboring specific HER2-activating mutations (DESTINY-PanTumor01).

Abstract #TPS3162

Poster Session

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

4 June 2021

Yoshino, T

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01).

Abstract #3505

Oral Abstract Session

Gastrointestinal Cancer—Colorectal and Anal

7 June 2021

Raghav, K

Trastuzumab deruxtecan in patients with HER2-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC): A randomized, multicenter, phase 2 study (DESTINY-CRC02).

Abstract #TPS3620

Poster Session

Gastrointestinal Cancer—Colorectal and Anal

4 June 2021

Jerusalem, G

Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: a subgroup analysis of the DESTINY-Breast01 trial.

Abstract #526

Poster Session

Breast Cancer— Local/Regional/Adjuvant

4 June 2021

Yamaguchi, K

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY-Gastric01).

Abstract #4048

Poster Session

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

4 June 2021

DNA damage response

Tutt, A

OlympiA: A phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high risk HER2-negative early breast cancer.

Abstract #LBA1

Plenary Session

6 June 2021, 1:00pm EDT

Liu, JF

ADAGIO: A phase IIb, open-label, single-arm, multicenter study assessing the efficacy and safety of adavosertib (AZD1775) as treatment for recurrent or persistent uterine serous carcinoma.

Abstract #TPS5612

Poster Session

Gynecologic Cancer

4 June 2021

Poveda, A

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

Abstract #5545

Poster Session

Gynecologic Cancer

4 June 2021

Matthews, CA

Olaparib treatment (Tx) in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Overall survival (OS) results from the phase II LIGHT study.

Abstract #5515

Poster Discussion Session

Gynecologic Cancer

4 June 2021

Pautier, P

Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial.

Abstract #5514

Poster Discussion Session

Gynecologic Cancer

4 June 2021

Haematology

Byrd, J

First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia.

Abstract #7500

Oral Abstract Session

Hematologic Malignancies

7 June 2021

Sharman, JP

Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Elevate-TN four-year follow up.

Abstract #7509

Poster Discussion Session

Hematologic Malignancies

4 June 2021

Sehn, L

ESCALADE: A phase 3 study of acalabrutinib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for patients ≤65y with untreated non-germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL).

Abstract #TPS7572

Poster Session

Hematologic Malignancies

4 June 2021

174 company-sponsored or supported abstracts will be presented at ASCO (Free ASCO Whitepaper) 2021.
2Beginning Friday 4 June 2021 09:00 EDT oral presentations, poster discussions and poster sessions will be available on demand for 180 days including video and slide presentations and discussant commentary.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On May 19, 2021 Seagen Inc.(Nasdaq:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported updated results from two clinical trials examining PADCEV (enfortumab vedotin-ejfv) alone (EV-201 Cohort 2) and PADCEV in combination with Merck’s (known as MSD outside the United States and Canada) KEYTRUDA (pembrolizumab) (EV-103 Cohort A) in patients with locally advanced or metastatic urothelial cancer who are not able to receive cisplatin chemotherapy (Press release, Seagen, MAY 19, 2021, View Source [SID1234580267]).

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"EV-201 Cohort 2 is the first study to report objective responses in patients with advanced urothelial cancer that progressed following immunotherapy and who have medical conditions that prevent them from receiving cisplatin chemotherapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "The analysis that will be presented at ASCO (Free ASCO Whitepaper) showed that after a median follow-up of 16 months, many patients continued to benefit from PADCEV – an important finding for these patients, who have very limited treatment options."

"EV-103 is the first clinical trial to combine the antibody-drug conjugate PADCEV with Merck’s anti-PD-1 therapy KEYTRUDA in patients newly diagnosed with locally advanced or metastatic urothelial cancer," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "The updated data from EV-103 Cohort A, with two years of follow-up, build upon findings from the initial analysis, showing continued durability for this platinum-free combination."

Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2(Abstract 4524)

Patients in Cohort 2 of EV-201 received prior treatment with an immunotherapy but had not received a platinum-containing chemotherapy in the locally advanced or metastatic setting and were ineligible for cisplatin chemotherapy.

With a median follow-up of 16 months, 51 percent of patients who received PADCEV had a confirmed objective response [95% Confidence Interval (CI): 39.8, 61.3] per blinded independent central review (the primary endpoint), with 22 percent of patients experiencing a complete response (CR). Median duration of response (DOR) was 13.8 months [95% CI: 6.4, not reached]. Patients lived a median of 6.7 months without cancer progression [progression-free survival (PFS) (95% CI: 5.0-8.3)] and had a median overall survival (OS) of 16.1 months (95% CI: 11.3, 24.1).

The most common all-grade treatment-related adverse events (TRAEs) were alopecia (51%), peripheral sensory neuropathy (49%) and fatigue (34%), and the most common Grade 3 or greater TRAEs were neutropenia (9%), maculopapular rash (8%) and fatigue (7%). Grade 3 or greater TRAEs of special interest included skin reactions (17%), peripheral neuropathy (8%) and hyperglycemia (6%). Four deaths were previously reported as treatment-related by investigators in patients age 75 years and older with multiple comorbidities.

The U.S. Food and Drug Administration (FDA) recently granted Priority Review to a supplemental application for PADCEV based on the primary analysis from EV-201 Cohort 2, which was published this month inThe Lancet Oncology.

Study EV-103: Update on durability results and long-term outcome of enfortumab vedotin + pembrolizumab in first-line locally advanced or metastatic urothelial carcinoma (la/mUC)(Abstract 4528)

In the dose-escalation cohort and expansion Cohort A in EV-103, patients were treated with a combination of PADCEV and the anti-PD-1 therapy KEYTRUDA as a first-line treatment for locally advanced or metastatic disease. Participants were ineligible for cisplatin-based chemotherapy, had no prior systemic treatment for locally advanced or metastatic disease, and did not receive adjuvant/neoadjuvant platinum-based therapy within 12 months prior to enrollment.

The primary outcome measure in this analysis was safety. With a median follow-up of 24.9 months, the longer-term analysis demonstrated a safety profile generally consistent with previous findings with no new safety signals observed. The most common TRAEs were peripheral sensory neuropathy (55.6%), fatigue (51.1%) and alopecia (48.9%), and the most common Grade 3 or greater TRAEs were increased lipase (17.8%), maculopapular rash (11.1%) and fatigue (11.1%). Grade 3 or greater TRAEs of interest included skin reactions (20%), hyperglycemia (8.9%) and peripheral neuropathy (4.4%). There was one death previously reported as possibly related to study treatment (multiple organ dysfunction syndrome).

As previously reported, results demonstrated an objective response rate of 73.3 percent (95% CI: 58.1, 85.4) per investigator assessment, with 15.6 percent of patients experiencing a CR. The median PFS was 12.3 months (95% CI: 8.0, not reached). With longer-term follow-up, the study showed a median DOR of 25.6 months (95% CI: 8.3, not reached) and median OS of 26.1 months (95% CI: 15.7, not reached).

The FDA granted Breakthrough Therapy designation last year for the PADCEV and KEYTRUDA combination for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

About Urothelial Cancer

Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.2

About the EV-201 Trial

The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (Cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (Cohort 2). The trial enrolled 128 patients in Cohort 1 and 91 patients in Cohort 2 at multiple centers internationally.1 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

About the EV-103 Trial

EV-103 (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of PADCEV alone or in combination, evaluating safety, tolerability and efficacy in muscle invasive urothelial cancer, and in locally advanced or metastatic urothelial cancer in first- or second-line settings.

The dose-escalation cohort and expansion Cohort A include locally advanced or metastatic urothelial cancer patients who are ineligible for cisplatin-based chemotherapy. Patients were dosed in a 21-day cycle, receiving an intravenous (IV) infusion of enfortumab vedotin on Days 1 and 8 and pembrolizumab on Day 1. At the time of the initial analysis, 45 patients (5 from the dose-escalation cohort and 40 from the dose-expansion Cohort A) with locally advanced and/or metastatic urothelial cancer had been treated with enfortumab vedotin (1.25 mg/kg) plus pembrolizumab in the first-line setting.

The primary outcome measure of the cohorts included in this analysis is safety. Key secondary objectives related to efficacy include objective response rate, disease control rate, duration of response, progression-free survival and overall survival.

Additional enrolling cohorts in the EV-103 study include:

PADCEV as monotherapy or in combination with pembrolizumab in a first-line setting for locally advanced or metastatic disease, in patients ineligible for cisplatin-based chemotherapy (Cohort K)
PADCEV as a monotherapy in muscle-invasive disease (Cohort L)
About PADCEV (enfortumab vedotin-ejfv)

PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA’s Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.3

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.3,4 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).4 PADCEV is co-developed by Astellas and Seagen.

PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information

Warnings and Precautions

Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Lab Abnormalities

In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

Drug Interactions

Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

On May 19, 2021 Incyte (Nasdaq: INCY) reported that multiple abstracts highlighting data from its oncology portfolio will be presented during the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held virtually from June 4-8, 2021 (Press release, Incyte, MAY 19, 2021, View Source [SID1234580283]).

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"We look forward to presenting data from across Incyte’s oncology portfolio and partner programs at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting," said Steven Stein, M.D., Chief Medical Officer, Incyte. "Data being presented during this congress, including new three-year data from the L-MIND study of tafasitamab in relapsed or refractory diffuse large B-cell lymphoma as well as results of the OPTIC study of ponatinib in chronic phase-chronic myeloid leukemia, underscore our continued focus on advancing science to help meet patients’ needs."

Key abstracts accepted by ASCO (Free ASCO Whitepaper) include:

Oral Presentations

Ponatinib

OPTIC Primary Analysis: A Dose-Optimization Study of 3 Starting Doses of Ponatinib (PON)1(Abstract #7000. Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant.)

Poster Discussions

Tafasitamab

Long-Term Analyses from L-MIND, a Phase 2 Study of Tafasitamab (MOR208) Combined with Lenalidomide (LEN) in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)2 (Abstract #7513. Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia.)

Capmatinib

Capmatinib in MET Exon 14-Mutated, Advanced NSCLC: Updated Results from the GEOMETRY Mono-1 Study3(Abstract #9020. Session: Lung Cancer—Non-Small Cell Metastatic.)

ePosters

Capmatinib

Capmatinib Efficacy in Patients with NSCLC Identified as METex14 Using an NGS-Based Liquid Biopsy Assay: Results from the GEOMETRY Mono-1 Study3(Abstract #9111. Session: Lung Cancer—Non-Small Cell Metastatic.)

Patient-Reported Outcomes in Capmatinib-Treated Patients with METex14-Mutated Advanced NSCLC: Results from the Phase 2 GEOMETRY Mono-1 Study3(Abstract #9056. Session: Lung Cancer—Non-Small Cell Metastatic.)

Phase 1b/2 Study of Capmatinib Plus Gefitinib in Patients with EGFR-Mutated, MET-Dysregulated Non–Small Cell Lung Cancer who Received Prior Therapy: Final Overall Survival and Safety3(Abstract #9048. Session: Lung Cancer—Non-Small Cell Metastatic.)

Pemigatinib

Pemigatinib for Previously Treated Locally Advanced/Metastatic Cholangiocarcinoma (CCA): Update of FIGHT-202 (Abstract #4086. Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary.)

Retifanlimab

Phase 2 Study of Retifanlimab (INCMGA00012) in Patients (Pts) with Selected Solid Tumors (POD1UM-203) (Abstract #2571. Session: Developmental Therapeutics—Immunotherapy.)

Ruxolitinib-Parsaclisib Combination Studies

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ruxolitinib Plus Parsaclisib in Patients with JAK- and PI3K-Inhibitor Treatment–Naïve Myelofibrosis (Abstract #TPS7058. Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant.)

Tafasitamab

A Phase 3 Study to Evaluate the Efficacy and Safety of Tafasitamab Plus Lenalidomide and Rituximab Versus Placebo Plus Lenalidomide and Rituximab in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) (Abstract #TPS7568. Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia.)

First-MIND: A Phase 1b, Open-Label, Randomized Study to Assess Safety of Tafasitamab (tafa) or Tafa + Lenalidomide (LEN) in Addition to R‑CHOP in Patients with Newly Diagnosed DLBCL2(Abstract #7540. Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia.)

For full session details and data presentation listings, please see the ASCO (Free ASCO Whitepaper)21 online program at View Source Oral, poster discussion and poster sessions, as well as track-based clinical science symposia, accepted for presentation at ASCO (Free ASCO Whitepaper) will be available on demand beginning Friday, June 4, 2021 at 9:00 a.m. ET.

On May 19, 2021 Susan G. Komen, the world’s leading breast cancer organization, reported a new integrated campaign, in partnership with Amgen, to educate the breast cancer community about the link between breast and bone health, providing useful information for women of all ages and stages of breast cancer (Press release, Amgen, MAY 19, 2021, View Source [SID1234580299]).

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"Breast cancer treatment can affect bone health, and it is one of main areas where breast cancers spread when they metastasize. Yet no matter your age, health or breast cancer diagnosis, your bone health may also be at risk," said Paula Schneider, president and CEO of Susan G. Komen and a breast cancer survivor. "Women have long known that it is important to understand what is normal for their breast health and to talk to their doctor if they notice any changes. Women need to include their bones in this moment of vigilance."

Metastatic breast cancer, also known as stage IV breast cancer, is when the breast cancer spreads beyond the breast and nearby lymph nodes to other parts of the body, often the bones. When breast cancer cells spread to the bones, lesions can occur that cause the bones to break easily and may result in spinal cord compression. Research shows that 70 percent of women with bone metastasis will have a skeletal related event within two years of diagnoses. All of these skeletal complications can lead to chronic pain and the loss of mobility.

Through a mixture of facts and personal storytelling, the integrated campaign will drive people to komen.org/breast-and-bone-health, where women will be provided useful information about their breast and bone health, including:

Questions to ask your doctor about metastatic breast cancer and bone protection
How to protect bones from fractures and other problems, including through diet
What treatments may negatively impact bone health
What drugs are available to improve bone density
Amgen also provides additional information for people living with metastatic breast cancer on its website – Let’s Talk Bone Mets.

Together, the two organizations seek to inspire people to learn more about their breast and bone health and become empowered to monitor their health and have constructive conversations with their health care teams.

On May 19, 2021 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported the upcoming presentation of updated results from the Company’s priority development pathways in head and neck cancer (head and neck squamous cell carcinoma; HNSCC) and in immunotherapy for advanced cancers at the 2021 Annual Meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Nanobiotix, MAY 19, 2021, View Source [SID1234580315]). The Company will also present a poster with long-term safety analysis from its pivotal phase II/III study in soft tissue sarcoma.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"The data we will present at ASCO (Free ASCO Whitepaper) provide further support for the paradigm-shifting potential of NBTXR3 as a foundational solid tumor-agnostic and combination-agnostic cancer therapeutic," said Laurent Levy, co-founder and chief executive officer of Nanobiotix. "We are excited to present both long-term safety data from our phase III soft tissue sarcoma study, along with updated safety and efficacy data from our second single-agent registration pathway in head and neck cancer. Moreover, we are particularly eager to present a growing body of data suggesting that after activation by radiotherapy, NBTXR3 may prime an immune response that could enhance the efficacy of immune checkpoint inhibitors as a first-line therapy, overcome resistance for refractory patients, and meaningfully expand the tumor types that respond to the class by transforming cold tumors into hot tumors."

Local Control as a Single-Agent for Patients with Head and Neck Cancer

Abstract #6051: Phase I Dose Expansion Study of Functionalized Hafnium Oxide Nanoparticles (NBTXR3) in Cisplatin-Ineligible Locally Advanced HNSCC Patients

The number of elderly patients diagnosed with locally advanced HNSCC (LA-HNSCC) is increasing. While concurrent chemoradiation is the non-surgical standard of care, not all patients can tolerate platinum-based chemotherapy (e.g., cisplatin). The Nanobiotix phase I dose expansion study in patients with LA-HNSCC (Study 102) is evaluating a single dose of NBTXR3 at 22% of baseline tumor volume (the recommended phase II dose; RP2D). Primary endpoints of the study are objective response rate (ORR) and complete response rate (CRR) of the primary tumor. Study 102 is expected to recruit a total of 44 evaluable patients. To date, 52 total patients have been injected with NBTXR3 in the study overall, of which 40 have been evaluable.

Updated data presented at ASCO (Free ASCO Whitepaper) further support NBTXR3 administration, followed by activation with radiotherapy, as feasible and well-tolerated. Six (6) serious adverse events (SAEs) related to NBTXR3 were observed across five (5) patients. A total of ten (10) deaths related to adverse events were reported. Four (4) deaths related to radiotherapy were observed, along with one (1) death from sepsis that was investigator-assessed as possibly related to NBTXR3, radiotherapy, and cancer.

At a median follow up of 8.1 months, evaluable patients demonstrated a high primary tumor ORR of 82.5% and a 62.5% CRR. These results are consistent with those observed in the dose escalation part of the study and suggest durability of efficacy.

Nanobiotix plans to launch a pivotal phase III global registration trial evaluating NBTXR3 as a single-agent activated by radiotherapy for patients with LA-HNSCC in 2021.

Priming Immune Response and Immunotherapy Combination Across Oncology

Abstract #2590: A Phase I Study of NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy
Abstract #2591: Overcoming Resistance to Anti-PD-1 with Tumor-Agnostic NBTXR3: From Bench to Bedside

Cancer immunotherapies such as anti-PD-1 have shown promising clinical outcomes over the past two decades and are often used to treat advanced cancers once other therapies have reached the end of their effectiveness. However, across tumor indications, the significant majority of patients (80-85% according to published data) receive only a temporary benefit from anti-PD-1—or no benefit at all—as they either develop resistance to the therapy over time or are non-responsive to treatment altogether.

Previously reported data from the Company’s phase I immunotherapy study in advanced cancers (Study 1100) and its preclinical collaboration with The University of Texas MD Anderson Cancer Center support NBTXR3 activated by radiotherapy as a potential primer of immune response. These data suggest that when combined with anti-PD-1, NBTXR3 could contribute to tumor regression in patients with advanced and metastatic tumors regardless of the patient’s prior exposure to anti-PD-1.

Nanobiotix will provide an update on Study 1100 with additional patients and further follow up prior to the conference (abstract #2590). The Company will also present a compilation of preclinical and clinical data supporting NBTXR3 as a potentially tumor-agnostic, therapeutic combination-agnostic agent that could overcome resistance to immune checkpoint inhibitors and increase response rates across tumor indications (abstract #2591).

Local Control as a Single-Agent for Patients with Soft Tissue Sarcoma

Abstract #11544: Long-Term Evaluation of the Novel Radioenhancer NBTXR3 plus Radiotherapy in Patients with Locally Advanced Soft Tissue Sarcoma Treated in the Phase III Act.in.Sarc Trial

A long-term safety analysis following the Nanobiotix phase II/III pivotal study evaluating NBTXR3 as a single-agent activated by radiotherapy in patients with locally advanced soft tissue sarcoma (STS) did not observe a negative impact on patient quality of life and long-term morbidity. The long-term safety profile of NBTXR3, together with its efficacy data, further supported a favorable benefit-risk ratio for patients with STS. The analysis highlighted potential for future indications, including non-resectable sarcoma, pediatric tumors, and re-irradiation.

Nanobiotix Investor Event

Nanobiotix will host a virtual investor event featuring several key opinion leaders, including study investigators, after the ASCO (Free ASCO Whitepaper) Annual Meeting on Friday, June 11, 2021 at 8 am ET. The discussion will expand on the new immunotherapy results from Study 1100 that will be reported prior to ASCO (Free ASCO Whitepaper), providing additional detail and clinical perspective, following the ASCO (Free ASCO Whitepaper) presentation. Register here.

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About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and a phase III global registrational study is planned to launch in 2021. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the planned phase III study.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company-sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.