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Merck Announces Findings from Phase 3 Study of KEYTRUDA® (pembrolizumab), Compared to Standard of Care, in Patients with Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

On September 11, 2017 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported results of the phase 3 KEYNOTE-040 trial investigating KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, compared to standard treatment (methotrexate, docetaxel or cetuximab) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy (Press release, Merck & Co, SEP 11, 2017, View Source [SID1234520493]).

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As previously disclosed, the study did not meet its pre-specified primary endpoint of overall survival (OS). The findings include updated survival data showing a 19 percent reduction in the risk of death over standard treatment in the intent-to-treat population (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204), with pre-specified p-value required for statistical significance of 0.0175, and a median OS of 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1 months with standard treatment (95% CI, 5.9-8.1). Complete results will be presented for the first time at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in Madrid, Spain, in an oral presentation today from 3:00 – 3:12 p.m. CEST (Location: Granada Auditorium) (Abstract #LBA45_PR).

"These data, including progression-free survival and overall response rate, show the activity and efficacy of pembrolizumab in this disease, and are consistent with prior studies of pembrolizumab in recurrent head and neck squamous cell carcinoma," said Ezra Cohen, M.D., associate director for translational science, Moores Cancer Center and co-director of the San Diego Center for Precision Immunotherapy, University of California, San Diego. "KEYNOTE-40 strengthens the rationale for further studies, and expansion into earlier lines of disease."

With more than 20 trials, Merck currently has the largest immuno-oncology clinical development program in head and neck cancer and is advancing multiple registration-enabling studies investigating KEYTRUDA (pembrolizumab) as monotherapy and in combination with other cancer treatments – including KEYNOTE-048 and KEYNOTE-412.

"Although the primary efficacy analysis did not show a statistically significant improvement in overall survival, these data add to the evolving science for KEYTRUDA in head and neck cancer," said Dr. Jon Cheng, associate vice president, Merck Research Laboratories.

Data in Second-Line Treatment Setting, KEYNOTE-040 (Abstract #LBA45_PR)

KEYNOTE-040 is a randomized, multi-center, phase 3 study investigating KEYTRUDA as a monotherapy (n=247) versus standard treatment (methotrexate, docetaxel or cetuximab) (n=248) in patients with recurrent or metastatic HNSCC (additional details on the trial design are provided below).

Data presented at ESMO (Free ESMO Whitepaper) are based on findings in the intent-to-treat population (n=495) and include analysis of efficacy endpoints based on PD-L1 expression using two measurements: PD-L1 CPS ≥1 (n=387) and PD-L1 TPS ≥50% (n=129). More than a third of patients in the intent-to-treat population went on to receive subsequent therapy, including 11 of 84 patients in the KEYTRUDA arm and 31 of 100 patients in the standard treatment arm who received subsequent treatment with an immune checkpoint inhibitor. Other subsequent treatments included chemotherapy, EGFR inhibitor, kinase inhibitor, other immunotherapy, and other treatments.

Data show that in the intent-to-treat population, the median OS was 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1 months with standard treatment (95% CI, 5.9-8.1) (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204); the 12-month OS rate was 37.3 percent with KEYTRUDA compared to 27.2 percent with standard treatment. Further analysis of the primary endpoint based on PD-L1 expression showed:

In patients with PD-L1 CPS ≥1, the median OS was 8.7 months with KEYTRUDA (95% CI, 6.9-11.4) and 7.1 months with standard treatment (95% CI, 5.7-8.6) (HR, 0.75 [95% CI, 0.59-0.95]; p = 0.0078); the 12-month OS rate was 40.1 percent with KEYTRUDA compared to 26.7 percent with standard treatment.
In patients with PD-L1 TPS ≥50%, the median OS was 11.6 months with KEYTRUDA (95% CI, 8.3-19.5) and 7.9 months with standard treatment (95% CI, 4.8-9.3) (HR, 0.54 [95% CI, 0.35-0.82]; p = 0.0017); the 12-month OS rate was 46.6 percent with KEYTRUDA compared to 25.8 percent with standard treatment.
The overall response rate (ORR) in the intent-to-treat population was 14.6 percent in the KEYTRUDA (pembrolizumab) arm compared to 10.1 percent in the standard treatment arm (p = 0.0610). In patients with PD-L1 CPS ≥1, the ORR was 17.3 percent with KEYTRUDA compared to 9.9 percent with standard treatment (p = 0.0171). In patients with PD-L1 TPS ≥50%, the ORR was 26.6 percent with KEYTRUDA compared to 9.2 percent with standard treatment (p = 0.0009).

The median progression-free survival (PFS) was 2.1 months in the intent-to-treat population with KEYTRUDA (95% CI, 2.1-2.3) and 2.3 months with standard treatment (95% CI, 2.1-2.8) (HR, 0.95 [95% CI, 0.79-1.16]; p = 0.3037). In patients with PD-L1 CPS ≥1, the median PFS was 2.2 months with KEYTRUDA (95% CI, 2.1-3.0) and 2.3 months with standard treatment (95% CI, 2.1-3.3) (HR, 0.89 [95% CI, 0.72-1.11]; p = 0.1526). In patients with PD-L1 TPS ≥50%, the median PFS was 3.5 months with KEYTRUDA (95% CI, 2.1-6.3) and 2.2 months with standard treatment (95% CI, 2.0-2.5) (HR, 0.58 [95% CI, 0.39-0.87]; p = 0.0034).

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Treatment-related adverse events (TRAEs) of any grade occurred in 155 patients (63.0%) in the KEYTRUDA arm and 196 patients (83.8%) in the standard treatment arm. Across any arm, TRAEs with incidence of 10 percent or more included hypothyroidism, fatigue, diarrhea, rash, asthenia, anemia, nausea, mucosal inflammation, stomatitis, decreased neutrophil count and alopecia. Immune-mediated adverse events, any grade, occurring in the KEYTRUDA arm were hypothyroidism, pneumonitis, infusion reactions, severe skin reactions, hyperthyroidism, colitis, Guillain-Barre syndrome and hepatitis. Discontinuation due to TRAEs occurred in 15 patients (6.1%) in the KEYTRUDA arm and 12 patients (5.1%) in the standard treatment arm. Deaths due to treatment-related adverse events occurred in four patients (1.6%) in the KEYTRUDA arm and two patients (0.9%) in the standard treatment arm.

About KEYNOTE-040

KEYNOTE-040 is a randomized, multi-center, pivotal phase 3 study investigating KEYTRUDA as a monotherapy versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic HNSCC. The primary endpoint is OS; secondary endpoints include PFS and ORR. The study, which opened in November 2014, enrolled 495 patients to receive KEYTRUDA (200 mg fixed dose every three weeks) or investigator-choice chemotherapy (methotrexate [40 mg/m2 on Days 1, 8, and 15 of each 3-week cycle], docetaxel [75 mg/m2 on Day 1 of each 3-week cycle], or cetuximab [400 mg/m2 loading dose on Day 1 and 250 mg/m2 IV on Days 8 and 15 of Cycle 1], followed by cetuximab [250 mg/m2 on Days 1, 8, and 15 of each subsequent 3-week cycle]). Patients enrolled in the study had been previously treated with one to two platinum-containing systemic regimens.

About KEYTRUDA (pembrolizumab) Injection 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Studies of KEYTRUDA – from the largest immuno-oncology program in the industry with more than 550 trials – include a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand factors that predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including the exploration of several different biomarkers across a broad range of tumors.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC, occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA (pembrolizumab) and administer corticosteroids. For signs and symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. These immune-mediated reactions may occur in any organ system. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA (pembrolizumab) on any trial, 6 patients (26%) developed graft-versus-host-disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor–blocking antibody before transplantation. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

When KEYTRUDA was administered in combination with carboplatin and pemetrexed (carbo/pem), KEYTRUDA was discontinued in 10% of 59 patients. The most common adverse reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute kidney injury (3.4%). Adverse reactions leading to interruption of KEYTRUDA (pembrolizumab) occurred in 39% of patients; the most common (≥2%) were fatigue (8%), neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and pneumonitis (3.4%).The most common adverse reactions (≥20%) with KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%), nausea (68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%), vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%), decreased appetite (31% vs 23%), headache (31% vs 16%), cough (24% vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%), peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia (20% vs 3.2%), upper respiratory tract infection (20% vs 3.2%), and arthralgia (15% vs 24%). This study was not designed to demonstrate a statistically significant difference in adverse reaction rates for KEYTRUDA as compared to carbo/pem alone for any specified adverse reaction.

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL, and treatment was interrupted due to adverse reactions in 26% of patients. Fifteen percent (15%) of patients had an adverse reaction requiring systemic corticosteroid therapy. Serious adverse reactions occurred in 16% of patients. The most frequent serious adverse reactions (≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; one from GVHD after subsequent allogeneic HSCT and one from septic shock. The most common adverse reactions (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reactions (in≥20% of patients) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients (5%) died from causes other than disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and 3 patients (0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA (pembrolizumab) occurred in 22% of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue, joint pain, and pneumonia. Serious adverse reactions occurred in 42% of patients, the most frequent (≥2%) of which were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Adverse reactions leading to interruption of KEYTRUDA occurred in 20% of patients; the most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%), and colitis (1.1%). The most common adverse reactions (20%) in patients who received KEYTRUDA vs those who received chemotherapy were fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients, the most frequent (≥2%) of which were urinary tract infection, pneumonia, anemia, and pneumonitis.

There is limited experience in pediatric patients. Efficacy for pediatric patients was extrapolated from the results in the adult cHL population. In a study of 40 pediatric patients with advanced melanoma, PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma, patients were treated with KEYTRUDA for a median of 43 days (range 1-414 days), with 24 patients (60%) receiving treatment for 42 days or more. The safety profile in pediatric patients was similar to that seen in adults treated with KEYTRUDA. Toxicities that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

BeiGene Presents Preliminary Phase 1 Data for BGB-A317 in Multiple Solid Tumors at the ESMO 2017 Congress

On September 11, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported preliminary data from multiple disease-specific subgroups in the ongoing Phase 1A/1B trial of its investigational anti-PD-1 antibody BGB-A317 in advanced solid tumors at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in Madrid, Spain (Press release, BeiGene, SEP 11, 2017, View Source [SID1234520492]).

The three posters contained preliminary data from patients with gastric cancer (GC) and esophageal cancer (EC), head and neck squamous cell carcinoma (HNSCC), and ovarian cancer (OC), respectively. The preliminary Phase 1 data suggest that BGB-A317 was generally well tolerated and exhibited preliminary evidence of anti-tumor activity in advanced patients with each of these tumor types. BeiGene recently closed its global strategic collaboration with Celgene Corporation, in which Celgene gained exclusive rights to develop and commercialize BGB-A317 for solid tumors in the United States, Europe, Japan, and the rest of the world outside of Asia, while BeiGene retains rights for solid tumors in Asia (excluding Japan), and for hematological malignancies and internal combinations globally.

"The early data in each of these patient populations are promising, with confirmed partial responses observed in all four cancer types. Adverse events reported in each group were consistent with the overall safety profile observed in the trial and were generally of low severity, manageable, and reversible," commented Jayesh Desai, MD, FRACP, a medical oncologist at The Royal Melbourne Hospital and Peter MacCallum Cancer Centre in Melbourne, Australia, and coordinating principal investigator of the study.

"We are pleased to provide early data on patients with four different cancer types enrolled in our global Phase 1 study of BGB-A317. The preliminary safety profile and antitumor activity support continued development of BGB-A317. BGB-A317 is in registrational trials in China for bladder cancer and classical Hodgkin lymphoma. We look forward to working with Celgene as we plan to initiate global registrational trials," commented Amy Peterson, MD, Chief Medical Officer, Immuno-oncology at BeiGene.

Trial Design

The multi-center, open-label Phase 1A/1B trial of BGB-A317 as monotherapy in advanced solid tumors is being conducted in Australia, New Zealand, the United States, Taiwan, and South Korea and consists of a Phase 1A component (dose-escalation, schedule-expansion, and fixed-dose expansion) and a Phase 1B component of indication expansion in disease-specific cohorts, which include GC, EC, HNSCC, and OC cohorts, among others. In the Phase 1A portion, the maximum administered dose was 10 mg/kg once every two weeks (Q2W) and the maximum tolerated dose was not reached. All patients in the Phase 1B portion received BGB-A317 as a 5 mg/kg intravenous infusion once every three weeks (Q3W). The data cutoff date for the presentations at ESMO (Free ESMO Whitepaper) was June 8, 2017.

Preliminary Results in GC and EC (Abstract #387P)

The data presented at ESMO (Free ESMO Whitepaper) were from 83 patients with advanced or metastatic GC (46 patients) or EC (37 patients) treated with BGB-A317 at 2 mg/kg or 5 mg/kg Q2W or Q3W. At the time of the data cutoff, median treatment duration was 45 days (range 4–457 days) for patients with GC and 50 days (range 1–246 days) for patients with EC.

Adverse events (AEs) assessed by the investigator to be related to treatment occurred in 15 patients with GC (33%). Of those, abdominal pain (9%), decreased appetite (9%), fatigue (7%), nausea (7%), and pruritus (4%) were reported in more than one patient, and all of these cases were grades 1 or 2. AEs assessed to be related to treatment occurred in 15 patients with EC (41%). Of those, fatigue (16%), nausea (8%), decreased appetite (5%), infusion-related reaction (5%), and myalgia (5%) occurred in more than one patient, and all of these cases were grades 1 or 2. Only one patient in each cohort reported a treatment-related AE of grade 3 or higher: grade 3 proteinuria in one patient with GC and grade 3 dermatitis in one patient with EC. Serious AEs (SAEs) considered related to treatment included one case of diarrhea and one case of pyrexia, each occurring in patients with GC. Eight patients (two with GC, six with EC) had a treatment-emergent AE with a fatal outcome, none were assessed as related to treatment.

At the time of the data cutoff, the efficacy-evaluable population (measurable disease at baseline and at least one post-baseline tumor assessment, or progression or death) included 34 GC patients and 31 EC patients. Among GC patients, four achieved a confirmed partial response (PR) and three achieved stable disease (SD) per RECIST 1.1 criteria. Among EC patients, two achieved a confirmed PR and nine achieved SD. Three of the nine patients with EC who achieved SD also achieved an unconfirmed PR, including one who awaits response confirmation. At the time of the data cutoff, 27 patients remained on treatment.

Preliminary Results in HNSCC (Abstract #388P)

The data presented at ESMO (Free ESMO Whitepaper) were from 18 patients with advanced HNSCC treated with BGB-A317 at 5 mg/kg Q3W. At the time of the data cutoff, median treatment duration was 104 days (range 30–339 days).

AEs assessed by the investigator to be related to treatment occurred in seven patients with HNSCC (39%). Of those, only fatigue (11%, all grade 1 or 2) was reported in more than one patient. One case of grade 3 nausea was the only treatment-related AE of grade 3 or higher in severity. No patient discontinued treatment due to a treatment-related AE, and of the nine deaths reported, none were considered to be associated with the treatment.

Of the 17 efficacy-evaluable HNSCC patients, three achieved a confirmed PR and six achieved SD. At the time of the data cutoff, three patients remained on treatment.

Preliminary Results in OC (Abstract #389P)

The data presented at ESMO (Free ESMO Whitepaper) were from 51 patients with advanced or metastatic OC treated with BGB-A317 at different dose levels (0.5 to 10 mg/kg Q2W in dose escalation, 2 or 5 mg/kg Q2W or Q3W or 200 mg Q3W in dose expansion, or 5 mg/kg Q3W in indication expansion). At the time of the data cutoff, median treatment duration was 71 days (range 29–540 days).

AEs assessed by the investigator to be related to treatment occurred in 28 patients (55%). Of those, fatigue (18%), pruritus (10%), rash (10%), diarrhea (10%), lethargy (6%), nausea (6%), abdominal pain (4%), dry eye (4%), dry skin (4%), onychoclasis (4%), and maculo-papular rash (4%) were reported in more than one patient, and all, except one case of grade 3 diarrhea, were grades 1 or 2. Two additional treatment-related AEs of grade 3 or higher included one case each of grade 3 pyrexia and stomatitis. SAEs considered related to treatment occurred in three patients and included one case each of pyrexia, colitis, and mucosal inflammation.

Of the 50 efficacy-evaluable OC patients, two achieved a confirmed PR and 20 achieved SD. At the time of the data cutoff, six patients remained on treatment.

About BGB-A317

BGB-A317 is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. BGB-A317 has high affinity and specificity for PD-1. It is differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells. BGB-A317 is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene have a global strategic collaboration for BGB-A317 for solid tumors.

Peregrine Pharmaceuticals Reports Financial Results for First Quarter of Fiscal Year 2018 and Recent Developments

On September 11, 2017 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and through its proprietary R&D pipeline, reported financial results for the first quarter of fiscal year (FY) 2018 ended July 31, 2017, and provided an update on its contract manufacturing operations, research and development programs, and other corporate highlights (Press release, Peregrine Pharmaceuticals, SEP 11, 2017, View Source [SID1234520488]).

Highlights Since April 30, 2017
"We have been working diligently toward the transformation from an R&D focused business to a business dedicated to a contract development and manufacturing organization or CDMO. The appointment of Roger Lias, Ph.D., as president of our CDMO subsidiary, Avid Bioservices, and his appointment to Peregrine’s board of directors marks an important next step in this transition. Roger is a highly experienced executive with a long track record of success in the CDMO industry, and was an ideal candidate for the position," stated Steven W. King, president and chief executive officer of Peregrine. "We have built a successful commercial CDMO business with an excellent regulatory track record and we look forward to taking Avid to the next level under Roger’s leadership. Naturally, job one will be a smooth transition to ensure we continue to support our existing clients while simultaneously working to attract new clients as we look to grow the business on multiple fronts."
Avid Bioservices was established as Peregrine’s internal biologics manufacturing and development group, and began formal operations in January 2002. Avid has grown from an internal support operation to a full service CDMO that manufactures bulk drug substance for products that are approved and marketed in over 18 countries by leading biopharma companies. Avid was recently recognized as a leading CDMO by Life Science Leader as a recipient of multiple 2017 Contract Manufacturing Leadership Awards for Quality, Reliability, Capabilities, Expertise and Compatibility. Avid has an outstanding regulatory inspection history and state-of-the-art cGMP manufacturing facilities. Mr. King has been president of Avid since its formation in addition to his role as president and CEO of Peregrine Pharmaceuticals since 2003.
Mr. King continued, "As we focus on the CDMO business, we have been evaluating the best option for divesting our R&D assets through licensing or asset sale. The goal being to find a partner that will make a significant short term investment in the bavituximab program in order to validate the subset analysis from the Phase III SUNRISE trial. The subset analysis, which supports the combination of bavituximab with checkpoint inhibitors, is compelling but needs further clinical validation. These data, combined with findings from our collaborators at Memorial Sloan Kettering Cancer Center (MSKCC) supporting combination with cellular therapy and the ongoing trials from our partners at the National Comprehensive Cancer Network (NCCN), have bolstered our drive to find a suitable partner for advancing the bavituximab and PS-exosome diagnostic programs. We are moving forward expeditiously as we recognize the need to move quickly from the R&D standpoint, as well as the establishment of a pure play CDMO with no R&D expenses. We hope to bring this process to completion over the coming months and will update you on our progress."
Avid Bioservices Highlights
"Avid had a strong first quarter, recognizing revenue of $27 million," stated Paul Lytle, chief financial officer of Peregrine. "When combined with a 57% decrease in R&D spending and a moderate decrease in SG&A, our net loss for the quarter decreased 89% to $1.2 million. During this transition year where we have seen a lower manufacturing demand from our top two customers, we are still expecting to generate between $50 and $55 million in revenue while we continue to focus on securing new customers and diversifying our customer base as we have added four new customers this calendar year thus far."
The company is providing manufacturing revenue guidance for the full FY 2018 of $50 million – $55 million.

Avid’s current manufacturing revenue backlog is $33 million, representing estimated future manufacturing revenue to be recognized under committed contracts. Most of the backlog is expected to be recognized during the remainder of FY 2018.
Research and Development Highlights
ASCO Highlights:
Peregrine researchers presented additional supportive data demonstrating that patients in the bavituximab containing arm who had low baseline PD-L1 expression on tumor cells (i.e., patients typically with poorer response to PD-1/PD-L1 checkpoint inhibitors) lived significantly longer than patients with high baseline PD-L1 expression.
ESMO Highlights:
Clinical investigators and Peregrine researchers presented the final clinical results from the company’s Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer.
As previously reported, study results demonstrated that the addition of bavituximab to docetaxel did not result in improvement of the study’s primary endpoint of overall survival in the intent-to-treat population. However, a subgroup analysis on the final dataset demonstrated that for bavituximab plus docetaxel patients who received subsequent immunotherapy, the median overall survival was not yet reached. This compared to a median overall survival of 12.6 months for patients who received placebo plus docetaxel, and subsequent immunotherapy [HR = 0.46; p = 0.006].
NCCN Highlights:
The three clinical trials under the collaboration with the NCCN are advancing as planned.
Massachusetts General Hospital Cancer Center—Phase I/II Clinical Trial of Bavituximab with Radiation and Temozolomide for Patients with Newly Diagnosed Glioblastoma. Patient dosing was initiated in September 2017.

Moffitt Cancer Center—A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy for Unresectable Hepatitis C Associated Hepatocellular Carcinoma. This trial is open for enrollment.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins—Phase II Study of Pembrolizumab and Bavituximab for Progressive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck. This trial is expected to be initiated by the end of the calendar year 2017.
PS Exosome Technology Highlights:
The company continues to make progress with its PS exosome diagnostic technology that is designed to detect and monitor cancer. The assay has been successfully optimized and we are evaluating options to license, partner, or sell this technology.
Financial Highlights and Results
Contract manufacturing revenue from Avid’s clinical and commercial biomanufacturing services was $27,077,000 for the first quarter of FY 2018 compared to $5,609,000 for the first quarter of FY 2017. This represents total revenue growth of 383% for FY 2018 compared to the same prior year period. It is important to note that the $27 million included the shipment of $10 million in product, which was held over from the fourth quarter of 2017 due to delays in shipping at the customer’s request. The first quarter increase was primarily attributed to an increase in demand for contract manufacturing services associated with process validation activities in addition to the greater number of manufacturing runs shipped during the quarter.

Total costs and expenses for the first quarter of FY 2018 were $28,306,000, compared to $16,691,000 for the first quarter of FY 2017. Research and development expenses decreased 57% to $3,645,000, compared to $8,569,000 for the first quarter of FY 2017.

Cost of contract manufacturing increased to $20,448,000 in the first quarter of FY 2018 compared to $3,062,000 for the first quarter of FY 2017. This increase is primarily due to an increase in the cost of contract manufacturing associated with higher reported revenue. Also contributing to this increase and impacting gross margins for the period was idle capacity due to lower demand and unavailable capacity during the installation of the new 2,000 liter bioreactors combined with a higher percentage of revenue related to pass through charges, such as raw materials, that are recorded as revenue at cost plus a nominal mark-up, thereby lowering the overall gross margin. During the current quarter, 38% of our revenue was related to pass-through charges versus 20% in the same prior year quarter.

For the first quarter of FY 2018, selling, general and administrative expenses decreased to $4,213,000 compared to $5,060,000 for FY 2017.

Peregrine’s consolidated net loss attributable to common stockholders was $2,647,000 or $0.06 per share, for the first quarter of FY 2018, compared to a net loss attributable to common stockholders of $12,437,000, or $0.36 per share, for the same prior year quarter.

Peregrine reported $37,256,000 in cash and cash equivalents as of July 31, 2017, compared to $46,799,000 at fiscal year ended April 30, 2017.
More detailed financial information and analysis may be found in Peregrine’s Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.

Onxeo Announces Top-Line Results from ReLive Phase III Study of Livatag® in Advanced Hepatocellular Carcinoma

On September 11, 2017 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), ("Onxeo" or the "Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs for the treatment of orphan diseases, in particular in oncology, reported top line results from the phase III ReLive trial of Livatag (doxorubicine Transdrug) in adult patients with unresectable hepatocellular carcinoma (HCC), intolerant to sorafenib or having progressed after a systemic therapy including sorafenib, when compared to best standard of care (Press release, Onxeo, SEP 11, 2017, View Source [SID1234520485]). The study did not meet its primary endpoint of improving survival over the comparative group.

The major reason is an unexpected high survival in the comparative group. Indeed, the study was not placebo controlled and patients in the comparative group could receive other anticancer agents (including oxaliplatin, gemcitabine or tyrosine kinase inhibitors) which might explain the high survival rate of the control arm. Livatag, as single agent, showed a similar effect as the one observed in that comparative group with active treatments. There was no difference in efficacy between the two arms (Livatag 20mg/m² and 30mg/m²).

The overall safety and tolerability profile of Livatag in ReLive was favorable with a fully manageable toxicity profile in both groups of Livatag (20mg/m² and 30mg/m²) including in those patients who underwent the longest treatment periods, over one year. The overall tolerability was comparable to the one observed in the comparative group.

"The Relive study did not meet its primary endpoint, partly due to the high survival rate in the control arm, which was unprecedented except in the most recent phase III negative trial post Sorafenib in HCC. However, Livatag tends to show a similar level of efficacy as recently reported for regorafenib in second line, in a well preserved liver function population (Child– Pugh A), although both drugs cannot be compared due to the lack of assessment of both drugs in the same trial." commented Philippe Merle, MD, Professor in Hepatology (La Croix Rousse Hospital, Lyon, France) and Coordinating Investigator of the ReLive study. "We want to thank all the investigators who have supported the completion of this large phase III trial as well as the patients and their families, and we are confident that they benefited in participating in the Relive study."

The monitoring of the patients still enrolled in the study will continue to completion expected in H1 2019.

The analysis of predefined subgroups is ongoing and the main results from the ReLive study will be presented on at the upcoming 11th Annual Conference of the International Liver Cancer Association in Seoul, South Korea (ILCA 2017 – ilca2017.org).

"Once the Relive data are fully analyzed, we will reinitiate licensing discussion with potential partners based on key study outcomes to define the best path forward", said Judith Greciet, Chief Executive Officer of Onxeo. "As already announced, Onxeo will continue to advance its diversified pipeline of innovative assets in oncology. Refocusing our R&D activities on AsiDNA and Beleodaq should extend our financial visibility until early 2020."

Daiichi Sankyo Presents New Data for DS-8201 in Multiple HER2-Expressing Solid Tumors at European Society for Medical Oncology (ESMO) 2017 Congress

On September 11, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), demonstrated preliminary antitumor activity in patients with HER2-expressing solid tumors such as colon cancer, non-small cell lung cancer and other tumor types (Press release, Daiichi Sankyo, SEP 11, 2017, View Source [SID1234520480]). These data were presented during a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in Madrid, Spain.

Preliminary results from the ongoing DS-8201 phase 1 study showed that DS-8201 demonstrated an overall confirmed response rate of 32 percent and a disease control rate of 82 percent in a subgroup analysis of 22 of 25 evaluable patients with HER2-expressing solid tumors, which included colon cancer (11 patients), non-small cell lung cancer (6 patients), salivary gland cancer (4 patients), Paget’s disease (2 patients), cholangiocarcinoma (1 patient) and esophageal cancer (1 patient). Two of 10 evaluable patients with colon cancer, one out of five evaluable patients with non-small cell lung cancer and three of four evaluable patients with salivary gland cancer achieved partial responses. Two additional patients with colon cancer and non-small cell lung cancer with one post baseline scan showed a partial response yet to be confirmed at subsequent scans. A total of 168 patients have been treated in both the dose escalation (24 patients) and dose expansion (144 patients) parts of the study as of August 1, 2017.

Safety data for 168 patients who received at least one dose of DS-8201 in study parts 1 and 2 and across different cohorts of the study also were reported. The most common adverse events (any grade) seen in all patients to date included nausea (67 percent), decreased appetite (56 percent), vomiting (33 percent), anemia (30 percent) and decreased platelet count (29 percent). Grade 3 adverse events occurring in >10 percent of patients included anemia (13 percent), decreased neutrophil count (14 percent) and decreased white blood cell count (11 percent). Grade 4 adverse events occurred in ≤ 3 percent of patients and included decreased platelet count (3.0 percent), decreased neutrophil count (2.4 percent), decreased white blood cell count (1.8 percent) and anemia (1.2 percent).

"These preliminary results are consistent with other data previously reported in the HER2-positive metastatic breast and gastric cancer cohorts of this study, demonstrating that further study is warranted for DS-8201 across other HER2-expressing solid tumors," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "These data add to the growing body of clinical evidence suggesting that DS-8201 could potentially become an important new treatment option for many different types of solid tumors that overexpress HER2. In addition to initiating our pivotal phase 2 study of DS-8201 in HER2-positive metastatic breast cancer, we are exploring next steps for the development of DS-8201 across multiple HER2-expressing tumor types."

About the DS-8201 Phase 1 Study
The open-label two-part phase 1 dosing study is currently evaluating DS-8201 in patients with advanced/
unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of the study was to assess the safety and tolerability of DS-8201 and determine the maximum tolerated dose. In the dose expansion part of the phase 1 study, DS-8201 is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2-positive advanced or metastatic breast cancer and gastric cancer, HER2 low-expressing breast cancer and other HER2-expressing solid tumors. Patient enrollment in the two breast cancer cohorts is ongoing in the U.S. and Japan. For more information about the study, please visit ClinicalTrials.gov.

About DS-8201
DS-8201 is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are a type of targeted cancer medicine that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker. It is designed to deliver enhanced cancer cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01), and in phase 1 development for HER2 low-expressing breast cancer, HER2-positive gastric cancer and other HER2-expressing solid tumors.
The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to DS-8201 for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1. DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established, and there is no guarantee DS-8201 will become commercially available.