On September 9, 2020 Roche reported that Tecentriq chalked up a surprising failure when used in tandem with chemotherapy paclitaxel in triple negative breast cancer (TNBC) (Press release, Hoffmann-La Roche, SEP 9, 2020, View Source [SID1234565000]). The FDA has taken notice, issuing a warning that might spell trouble for a conditional nod of the PD-L1 agent.

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On Tuesday, the FDA alerted the public that the Tecentriq-paclitaxel combo didn’t work in a clinical trial in previously untreated locally advanced or metastatic TNBC and warned doctors not to use it.

The thing is, Tecentriq already holds a similar approval in TNBC, which it won in March 2019—and it’s that nod that could be in jeopardy. "Continued approval … may be contingent on proven benefit of the treatment in additional trials," the FDA said.

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Tecentriq’s green light, restricted to PD-L1-expressing cases, is for a combination with Celgene’s Abraxane, or paclitaxel protein-bound, a formulation where paclitaxel is bound to albumin nanoparticles in a delivery mechanism that helps the drug concentrate in areas of tumor.

That conditional approval was based on data from the phase 3 IMpassion130 study, which showed that Tecentriq-Abraxane cut the risk of disease worsening or death by 40% over Abraxane alone in PD-L1-positive, previously untreated TNBC patients.

RELATED: Roche swings and misses with another Tecentriq-chemo combo in tough-to-treat breast cancer

However, in the phase 3 IMpassion131 trial, adding Tecentriq to paclitaxel didn’t stall tumor progression in newly diagnosed PD-L1-positive patients. To make it worse, interim results even favored solo paclitaxel in terms of life extension, though Roche said the data were not conclusive.

Based on the latest trial failure, the agency said it would review the findings and announce any changes to Tecentriq’s prescribing information.

In a statement, a spokesperson at Roche’s Genentech declined to comment on whether the IMpassion131 failure might affect Tecentriq’s approved TNBC use, only saying the company is in active discussions with the FDA.

Of course, IMpassion131 might not threaten the existing indication after all. First, compared with conventional paclitaxel, Abraxane is linked to preferential uptake into cancer cells and, hence, potentially offers a better anti-tumor effect thanks to its unique delivery tech.

Plus, I-O drugs have put up failures in confirmatory trials before, but so far none have led to the FDA terminating an approval. Tecentriq itself in 2017 flopped a phase 3 trial in previously untreated bladder cancer, but it still got to keep a go-ahead based on phase 2 tumor response data. In June, Merck & Co.’s rival PD-1 drug Keytruda, whether on its own or used in combination with chemotherapy, also failed to significantly keep bladder tumors at bay compared with chemo. But that drug may not lose its conditional approval, either; there’s no word yet from the FDA.

On September 9, 2020 The National Institute for Heath and Care Excellence (NICE) reported that it has turned down NHS funding of Revlimid (lenalidomide) as maintenance treatment after an autologous stem cell transplant for newly diagnosed multiple myeloma in adults (Press release, Celgene, SEP 9, 2020, View Source [SID1234564993]).

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There is currently no maintenance treatment for newly diagnosed multiple myeloma in people who have had an autologous stem cell transplant; the condition is usually monitored until it gets worse.

Clinical trial results show that, compared with monitoring alone, Revlimid increases how long people live and also extends the time before the condition gets worse.

However, NICE has concluded in preliminary guidelines that cost-effectiveness estimates for the drug in this setting "are uncertain".

"This is because of limitations in the cost-effectiveness model, and because the model might not reflect what happens in the NHS in England," it said.

Therefore, Revlimid could not be considered value for money for the NHS when used for this indication, it noted.

On September 9, 2020 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that a clinically meaningful 40% overall response rate (ORR) was observed in the subset of refractory multiple myeloma patients deemed triple class refractory who received a total administered dose of 60 mCi or greater (Press release, Cellectar Biosciences, SEP 9, 2020, View Source [SID1234564949]). Triple class refractory is defined as patients refractory to immunomodulatory, proteasome inhibitors and anti-CD38 antibody drug classes.

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The 40% ORR (6/15 patients) represents triple class refractory patients enrolled in Part A of Cellectar’s CLOVER-1 study and additional patients enrolled in Part B from March through May 2020. As a reminder, all patients being enrolled in Part B are required to be triple class refractory. The additional six patients were heavily pre-treated with an average of 9 prior multi-drug regimens. Three patients received a total administered dose of greater than 60 mCi and three received less than 60 mCi. Consistent with the data released in February 2020, patients receiving greater than 60 mCi exhibit strong responses. Patients continue to tolerate CLR 131 well, with the most common and almost exclusive treatment emergent adverse events being cytopenias and importantly, no unexpected adverse events have been reported.

"We remain encouraged by the consistency of CLR 131’s efficacy and tolerability data in these extremely challenging to treat triple class refractory multiple myeloma patients," said Dr. John Friend, CMO of Cellectar Biosciences. "A 40% ORR is a clinically meaningful outcome. For reference purposes, two recently approved drugs received a 25% and 31% ORR in triple class refractory patients. We look forward to the further development of CLR 131, a first in class phospholipid radio conjugate that may provide a significant benefit to patients and treatment alternative for clinicians."

About CLOVER-1

The Phase 2 CLOVER-1 study is an open-label study designed to determine the efficacy and safety of CLR 131 in select B-cell malignancies. The CLOVER-1 Phase 2 study completed the Part A dose-exploration portion, conducted in relapsed/refractory (r/r) B-cell malignancies, and is now enrolling in the Part B expansion cohorts evaluating ≥ 60 mCi total body dose and 2 cycle doses as patients have demonstrated a clinically meaningful response and predictable safety profile of CLR 131 in r/r multiple myeloma (MM) and lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia (LPL/WM). Patients with LPL/WM must have received at least two prior treatment regimens, unless ineligible to receive standard agents, and have measurable disease, as defined by either a nodal lesion of >15 mm, an extranodal lesion of >10 mm, or measurable IgM. Prior external beam radiation therapy was allowed. The median age of the four LPL/WM patients enrolled in the study was 70 (range 54-81) and included 2 females and 2 males who had a median of two prior regimens (range 1-5). CLR 131 was administered intravenously, up to 30 minutes.

Cellectar was awarded approximately $2 million in non-dilutive grant funding from the National Cancer Institute to help fund the study. More information about the study, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About CLR 131

CLR 131 is a small-molecule Phospholipid Drug Conjugate designed to provide targeted delivery of iodine-131 (radioisotope) directly to cancer cells, while limiting exposure to healthy cells unlike many traditional on-market treatment options. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-cell lymphomas, and a Phase 1 dose-escalating clinical study in pediatric solid tumors and lymphomas. The company recently completed a Phase 1 dose-escalation clinical study in r/r multiple myeloma. The FDA granted CLR 131 Fast Track Designation for both r/r multiple myeloma and r/r diffuse large B-cell lymphoma and Orphan Drug Designation (ODD) for the treatment of multiple myeloma, lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia, neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. CLR 131 was also granted Rare Pediatric Disease Designations for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. Earlier this year, the European Commission granted an ODD for r/r multiple myeloma and most recently, the U.S. Food and Drug Administration granted Fast Track Designation for CLR 131 in lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia (WM) in patients having received two prior treatment regimens or more.

On September 9, 2020 PDL BioPharma, Inc. ("PDL" or the "Company") (Nasdaq: PDLI) reported the closing of the sale of its wholly owned subsidiaries Noden Pharma DAC and Noden Pharma USA (collectively "Noden") to Stanley Capital (Press release, PDL BioPharma, SEP 9, 2020, View Source [SID1234564915]). The total value of the transaction will result in payments to PDL of up to $52.83 million in cash, $4.58 million greater than previously announced .

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"After running an extensive process, we are excited about closing this transaction with Stanley Capital," commented PDL’s President and CEO Dominique Monnet. "It represents the completion of a key divestiture for PDL and an exciting opportunity for the Noden team."

Payments to PDL, in connection with the closing of the transaction, are $12.72 million. The agreement provides for an additional $33 million to be paid to PDL in 12 equal quarterly installments from January 2021 to October 2023 and two potential contingent payments totaling $3.25 million. There is an additional $3.86 million to be paid to PDL in four equal quarterly installments from January 2023 to October 2023, primarily due to the incremental cash accumulated in the business since July 31, 2020.

Together with their advisors, Torreya and SVB Leerink, PDL’s board of directors and management team evaluated a number of potential transactions to maximize stockholder value for Noden. Torreya was retained by PDL to explore potential strategic transactions and assist in the disposition of Noden, while SVB Leerink has been engaged by PDL to advise on overall liquidation and distribution strategies.

In addition to the cash proceeds from the sale to Stanley Capital, PDL believes that this transaction may qualify for some Federal tax benefit under the CARES Act. In connection with its monetization process, PDL expects to execute transactions in 2020 that may result in the recognition of ordinary tax losses that, under the CARES Act, could be applied to prior tax years in which PDL was a substantial tax payor. At this time, however, there can be no assurance that such tax benefits will be realized.

On September 9, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported further STRO-002 updated interim Phase 1 safety and preliminary efficacy data in ovarian cancer, and an upcoming presentation at the 2020 xDigital Annual Global Meeting of the International Gynecologic Cancer Society (IGCS) on Sept. 10, 2020 (Press release, Sutro Biopharma, SEP 9, 2020, View Source [SID1234564912]).

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The interim clinical data from this dose escalation study evaluating the anti-folate receptor alpha (FolRα) antibody drug-conjugate (ADC) STRO-002 included 34 patients treated at 2.9 mg/kg and higher dose levels, with an overall response rate of 24% in 33 evaluable patients with post-baseline scans, with durability of 44% of patients on treatment for 16 weeks or greater and 12% of patients on treatment for 1 year or greater. The results announced today are based on a data cut-off date of Aug. 31, 2020, with 39 patients having been enrolled in the dose escalation study.

"We are pleased to observe improved efficacy outcomes as our data mature with longer follow-up, and the observed rate of objective response, stable disease and overall disease control during this study suggest that STRO-002 is potentially superior to other targeted ADC therapies being studied currently in ovarian cancer," said Dr. Arturo Molina, Chief Medical Officer of Sutro Biopharma. "Taken together with the optimized design approach to ADC safety, we believe that STRO-002 will be a potent and well-tolerated treatment option for patients. Next up, we plan to initiate a dose expansion trial in patients with less heavily pretreated ovarian cancer in the fourth quarter of 2020."

The interim clinical data for STRO-002 in patients evaluable for RECIST response include eight patients with partial responses. Seven patients with partial responses and 13 patients with stable disease achieved a disease control rate of 60% at 12 weeks or greater. STRO-002 continued to be well-tolerated and 87% of all treatment-emergent adverse events (AEs) were Grade 1 or 2; prophylactic corticosteroid eye drops have not been required. The most common Grade 3 and 4 AE was reversible neutropenia, with neuropathy and arthralgia observed at higher doses.

"We continue to see an encouraging efficacy and safety profile for STRO-002 in this heavily pretreated patient population," said Wendel Naumann, M.D., gynecologic oncologist at Levine Cancer Institute and a principal investigator on the STRO-002 study. "While Sutro plans to explore further dose optimization during dose expansion in a less heavily pre-treated patient population, we anticipate that the optimized therapeutic window and the recommended Phase 2 dose will be in the 4.3 to 5.2 mg/kg range. There is a tremendous unmet need for effective treatments in patients with advanced platinum-resistant and refractory epithelial ovarian cancer and we look forward continuing this study to explore the use of STRO-002 in treating this disease."

The Phase 1, open-label, multicenter, dose escalation trial with dose expansion of STRO-002 has completed enrollment and ongoing follow-up and will continue to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian or primary peritoneal cancer, and endometrial cancer. The trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF cell-free protein synthesis and XpressCF+ site-specific conjugation technologies.

Conference Call Information:
To access the conference call and live audio webcast on Wednesday, Sept. 9, at 5:30 p.m. EDT, please dial (877) 407-8974 (domestic) or (201) 389-0894 (international).

The conference call will be webcast via the Investors page on the Company’s website at ir.sutrobio.com. Approximately two hours following the live event, a webcast replay of the conference call will be available through the Company Presentation page of the Investor section of the company’s website at www.sutrobio.com for approximately 30 days.

Presentation Details:

Title:

Phase 1 Dose-Escalation Study of STRO-002, an anti-Folate Receptor alpha (FRα) Antibody Drug Conjugate (ADC), in Patients with Advanced Platinum-Resistant/Refractory Epithelial Ovarian Cancer (OC)

Abstract Number:

138 IGCS20_1113

Date/Time:

Sept. 10-13, 2020

Presenter:

Wendel Naumann, M.D.

The e-poster presentation can be found on the IGCS Meeting website and is also accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of Sutro Biopharma’s website at www.sutrobio.com on the day of the poster presentation.