On September 11, 2023 CymaBay Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing innovative therapies for liver and other chronic diseases with high unmet medical need, reported the pricing of its previously announced underwritten public offering of common stock and pre-funded warrants (Press release, CymaBay Therapeutics, SEP 11, 2023, View Source [SID1234635081]). CymaBay is selling 12,551,080 shares of common stock and, in lieu of common stock to certain investors, pre-funded warrants to purchase 583,771 shares of common stock in the offering. The shares of common stock are being sold at a public offering price of $17.13 per share, and the pre-funded warrants are being sold at a public offering price of $17.1299 per underlying share. The gross offering proceeds to CymaBay from this offering are expected to be approximately $225 million, before deducting the underwriting discount and other estimated offering expenses, and excluding the exercise of any pre-funded warrants. The pre-funded warrant has an exercise price of $0.0001 per share. All shares of common stock and pre-funded warrants to be sold in the offering are being offered by CymaBay. CymaBay has granted the underwriters a 30-day option to purchase up to an additional 1,970,227 shares of its common stock at the public offering price per share less underwriting discounts and commissions. The offering is expected to close on September 14, 2023, subject to the satisfaction of customary closing conditions.

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CymaBay anticipates using the net proceeds from the offering to fund ongoing development of seladelpar, including clinical trials targeting market expansion, and for working capital and general corporate purposes.

Piper Sandler, Raymond James, Cantor and LifeSci Capital are acting as the joint book-running managers for the offering. BTIG is acting as the lead manager for the offering.

The securities described above are being offered by CymaBay pursuant to a shelf registration statement filed with the Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement and accompanying prospectus related to the offering has been filed, and a final prospectus supplement and accompanying prospectus related to the offering will be filed, with the SEC and are or will be available on the SEC’s website at www.sec.gov. Copies of the prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, from: Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by telephone at (800) 747-3924, or by email at [email protected]; Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, by telephone at (800) 248-8863, or by e-mail at [email protected]; Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, New York 10022, or by e-mail at [email protected]; or LifeSci Capital LLC, Attention: Syndicate Prospectus Department, 250 West 55th Street, 34th Floor, New York, NY 10019, by email at [email protected] or by telephone at (646) 876-5059.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On September 11, 2023 PeproMene Bio, Inc., a clinical-stage biotech company developing novel therapies to treat cancers and immune disorders, reported that the first dose cohort of its phase 1 relapsed or refractory B-cell Non-Hodgkin Lymphoma (r/r B-NHL) clinical trial of PMB-CT01 (BAFFR-CAR T Cells) has been completed (Press release, PeproMene Bio, SEP 11, 2023, View Source [SID1234635080]). No Dose Limiting Toxicity (DLT) was observed, and the study has been cleared to proceed with the next cohort.

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The PMB-102 trial is taking place at City of Hope, one of the largest cancer research and treatment organizations in the nation. PeproMene licensed intellectual property relating to PMB-CT01 from City of Hope, which developed the therapy.

In the first cohort, administration of 50×106 PMB-CT01 has been extremely well tolerated. Among three treated patients, all three experienced only grade 1 cytokine release syndrome ("CRS") and two had grade 1 immune effector cell-associated neurotoxicity syndrome ("ICANS") with full recovery. The Overall Response Rate is 100% (two Complete Response and one Partial Response) at one-month post treatment. Two patients with mantle cell lymphoma had progressed after conventional CD19 CAR T-cell treatment prior to enrollment on PMB-CT01.

"We are pleasantly surprised and thrilled to see such minimal toxicity associated with such a high response rate in heavily pretreated patients who have failed 3-10 prior lines of therapy, including FDA-approved CD19 CAR T-cells", said Elizabeth Budde, M.D., Ph.D., the principal investigator of this single-center, dose escalation trial (NCT05370430) and associate professor at City of Hope, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation.

"Despite high initial efficacy of CD19-CAR T cell therapy for B-cell lymphoma and leukemia, a significant number of patients still relapse after CD19-CAR T treatment, highlighting the urgent unmet medical need," said Larry W. Kwak, M.D., Ph.D., vice president and deputy director of City of Hope’s Comprehensive Cancer Center and PeproMene’s scientific founder and compensated chair of its Scientific Advisory Board. Kwak has an equity interest in PeproMene. "Unlike CD19, BAFF-R signaling is required for B cell growth and survival, so it may limit the capacity of B cell tumors to evade therapy by loss of BAFF-R expression. I hope BAFFR-CAR T therapy will offer a clinically meaningful, new option for patients."

"Although still in early stage, we are encouraged by the initial observation of acceptable safety and preliminary efficacy in the first dose cohort of PMB-CT01 treated B-NHL patients. All 3 treated patients (2 progressed after CD19 CAR T therapy and 1 with CD19/CD20 negative lymphoma) responded to PMB-CT01 treatment," said Hazel Cheng, Ph.D., COO of PeproMene. "These clinical outcomes are consistent with City of Hope preclinical research data published in Science Translational Medicine in 2019, which showed that PMB-CT01 (BAFFR-CAR T Cells) could overcome CD19 antigen loss in B-cell malignancies."

About PMB-CT01

PMB-CT01 is a first-in-class BAFFR-targeted, autologous CAR T cell therapy. BAFF-R (B Cell Activating Factor Receptor), a tumor necrosis factor (TNF) receptor superfamily member, is the main receptor for BAFF expressing almost exclusively on B cells. Since BAFF-R signaling promotes normal B-cell proliferation and appears to be required for B-cell survival, it is unlikely tumor cells could escape immune responses via loss of BAFF-R antigen. This unique characteristic makes BAFF-R CAR T therapy a great potential treatment of B cell malignancies. BAFF-R CAR-T was constructed using the anti-BAFF-R scFv (single-chain fragment variable) antibodies with the 2nd generation signaling domains containing CD3ζ and 4-1BB. Our research has found that BAFFR-CAR T cells kill human lymphomas and leukemias in vitro as well as in animal models. PeproMene has licensed intellectual property relating to PMB-CT01, from City of Hope.

On September 11, 2023 Medivir AB (NASDAQ Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that Medivir’s partner Tango Therapeutics has received FDA clearance on its Investigational New Drug application for TNG348 (Press release, Medivir, SEP 11, 2023, View Source [SID1234635078]).

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TNG348 is a novel USP1 (ubiquitin-specific protease 1) inhibitor for the treatment of BRCA1/2-mutant and other homologous recombination deficiency (HRD)+ cancers. HRD+ cancers, including BRCA1/2 mutations, represent up to 50% of ovarian cancers, 25% of breast cancers, 10% of prostate cancers and 5% of pancreatic cancers.

Tango Therapeutics intends to initiate a phase 1 / 2 study with TNG348 in first half of 2024, both as single agent and in combination with a PARP-inhibitor. Preclinical data has shown synergistic effect with PARP inhibitors in PARP naïve models and that TNG348 is active in models with resistance to PARP inhibitors. These data suggest that TNG348 may benefit patients both as single agent or in combination with PARP inhibitors.

TNG348 is a USP-1 inhibitor developed from the preclinical USP-1 program in-licensed from Medivir in 2020.

Under the licensing agreement, Medivir is entitled to multiple development and commercial milestone payments as well as royalties on future sales.

"It is very encouraging to see another preclinical molecule developed by Medivir being evaluated in patients. The preclinical data generated by Tango Therapeutics looks very promising and we will be following the clinical development of TNG348 with great anticipation," says Jens Lindberg, CEO of Medivir.

For additional information, please contact;
Magnus Christensen, CFO, Medivir AB
Telephone: +46 8 5468 3100. E-mail: [email protected]

On September 11, 2023 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported initiation of a Phase 1 monotherapy expansion in the first-in-human clinical trial evaluating IDE161 (NCT 05787587) (Press release, Ideaya Biosciences, SEP 11, 2023, View Source [SID1234635077]).

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"We are pleased to advance IDE161, a potential first-in-class PARG inhibitor, into an expansion phase of our Phase 1 clinical trial and are excited to explore its potential in cancer patients with homologous recombination deficiency (HRD). Based on extensive preclinical studies, we are focusing this expansion in several priority tumor types, including ER+, Her2(-) breast cancer and ovarian cancer subjects with tumors that harbor HRD," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"The clinical update today on IDE161 represents the first reported preliminary clinical proof-of-concept for a PARG inhibitor in HRD solid tumors. We look forward to the continued evaluation of IDE161 as a monotherapy in high unmet medical need HRD solid tumor indications," said Yujiro S. Hata, Chief Executive Officer, IDEAYA Biosciences.

The Phase 1 first-in-human clinical trial is evaluating the safety, tolerability, pharmacokinetic and pharmacodynamic properties and preliminary efficacy of IDE161 in patients having tumors with homologous recombination deficiency (HRD). Early clinical data from the dose escalation cohorts showed dose-dependent pharmacodynamic modulation of poly-ADP ribose (PAR) proteins in peripheral blood, demonstrating IDE161 target engagement. These clinical data also demonstrated IDE161 exposure levels in humans which correlate to preclinical exposures that were efficacious, achieving tumor regressions in xenograft models.

The Phase 1 expansion is based on preliminary tumor shrinkage observed in multiple HRD solid tumor patients, including an BRCA1/2 endometrial cancer subject with a first imaging assessment of a partial response in the target lesion, a complete response in the non-target lesion and an 87% reduction in the CA-125 tumor marker (2,638 units/ml at baseline to 360 units/ml at 6-weeks). The company is also continuing to evaluate the optimal move forward dose for Phase 2 expansion. The expansion portion of the Phase 1 trial will include patients having HRD-associated breast cancer and ovarian cancer, as well as a basket of other selected solid tumors. The breast cancer focus is on estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (Her2-), HRD+ tumors, which represent approximately 10% to 14% of breast cancer patients. The ovarian cancer focus represents approximately 50% of ovarian cancer where HRD is observed. IDEAYA is targeting clinical program updates for IDE161 in the second half of 2023.

IDE161 is a potent, selective, small-molecule inhibitor of PARG, a novel and mechanistically-differentiated target in the same clinically validated pathway as poly (ADP-ribose) polymerase (PARP). IDEAYA presented a poster with preclinical data profiling IDE161 at the 2023 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April 2023. The IDE161 poster is available online at the company’s website at View Source

IDEAYA owns or controls all commercial rights in IDE161, subject to certain economic obligations under its exclusive, worldwide license with Cancer Research UK and University of Manchester.

On September 11, 2023 The Janssen Pharmaceutical Companies of Johnson & Johnson reported follow-up results from the Phase 1b/2 CHRYSALIS-2 study cohort evaluating the safety and tolerability of the combination of RYBREVANT (amivantamab-vmjw), a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), with lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI), plus platinum-based chemotherapy (carboplatin and pemetrexed) in patients with relapsed/refractory non-small cell lung cancer (NSCLC) and EGFR mutations (Press release, Johnson & Johnson, SEP 11, 2023, View Source [SID1234635076]). These findings are being presented at the International Association for the Study of Lung Cancer (IASLC) 2023 World Congress on Lung Cancer (WCLC) from September 9-12 in Singapore.1

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"Often, patients with EGFR-mutated NSCLC develop resistance to treatment during the course of therapy. Resistance in patients is typically diverse and polyclonal, meaning their tumors can have more than one type of resistance caused by different pathways. These variables can make their disease much harder to control and treat with targeted therapy alone," said Se-Hoon Lee,* M.D., Ph.D., professor of medicine at the Samsung Medical Center and Sungkyunkwan University School of Medicine and presenting author. "These long-term follow-up data from the CHRYSALIS-2 study in patients with previously treated EGFR-mutated NSCLC demonstrate the importance of treatment strategies that combine chemotherapy with targeted therapy to better address complex resistance patterns after treatment with third-generation EGFR TKIs."

CHRYSALIS-2 (NCT04077463) is an ongoing, multicohort, clinical study evaluating RYBREVANT in combination with lazertinib in patients with advanced NSCLC with EGFR exon 19 deletion mutations (ex19del) or L858R activating mutations.2 One cohort of CHRYSALIS-2 evaluated the combination of RYBREVANT and lazertinib with platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC who experienced disease progression on EGFR TKIs, a regimen similar to the one being evaluated in the ongoing MARIPOSA-2 study. Results from the RYBREVANT, lazertinib and chemotherapy combination cohort (n=20), were featured in a mini oral presentation (Abstract #MA13.06) at the IASLC 2023 WCLC. Enrolled patients received a median of two prior lines of therapy. Prior therapies included osimertinib (70 percent) and first- and second-generation EGFR TKIs (45 percent).1

The combination of RYBREVANT and lazertinib with chemotherapy yielded an objective response rate of 50 percent, with 11 out of 20 patients remaining on treatment. Median duration of response was not reached after a median follow-up of 13.1 months. Median progression-free survival (PFS) was 14 months. Eight of 10 responders had a response duration of at least six months. Five patients were treated beyond progression, with a median incremental treatment duration of 4.2 months. The most common treatment-emergent adverse events included low white blood cell count (neutropenia; 90 percent), rash (75 percent) and infusion-related reactions (65 percent).1

"The strong anti-tumor activity of RYBREVANT in EGFR-driven cancers reinforces the utility of this targeted, bispecific therapy in patients whose tumors are resistant," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "These results provide important insights into the treatment of patients with advanced non-small cell lung cancer with EGFR-mutated disease who have progressed on the current standard of care. We look forward to upcoming late-stage Phase 3 study readouts."

About the CHRYSALIS-2 Study
CHRYSALIS-2 (NCT04077463) is an open-label Phase 1/1b study to evaluate the safety and pharmacokinetics of lazertinib, a third generation EGFR-TKI, as monotherapy or in combination with RYBREVANT, a human bispecific EGFR and c-MET antibody in participants with advanced NSCLC. The study enrolled 460 patients with advanced NSCLC.2

About RYBREVANT
RYBREVANT (amivantamab-vmjw) received accelerated approval by the U.S. Food and Drug Administration (FDA) in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.3 This indication is approved under accelerated approval based on overall 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. RYBREVANT has also received approval from health authorities in Europe, as well as other markets around the world.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer◊ prefer NGS-based strategies over PCR-based approaches for the detection of EGFR exon 20 insertion variants and include amivantamab-vmjw (RYBREVANT) as a subsequent therapy option with a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.4†^

In addition to the Phase 1b/2 CHRYSALIS-2 study, RYBREVANT is being studied in multiple clinical trials in NSCLC, including:

The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT in combination with lazertinib, a novel third generation EGFR TKI, versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.5
The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib. Topline data for this randomized Phase 3 study demonstrated statistically significant and clinically meaningful improvement in PFS in these patients receiving RYBREVANT plus chemotherapy with and without lazertinib versus chemotherapy.6
The Phase 3 PAPILLON (NCT04538664) study assessing amivantamab in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Topline data for this randomized Phase 3 study demonstrated statistically significant and clinically meaningful improvement in PFS in patients receiving RYBREVANT.7
The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab SC delivery.8
The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.9
The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in participants with EGFR-mutated advanced or metastatic NSCLC.10
The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT and capmatinib combination therapy in locally advanced or metastatic NSCLC.11
The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT and cetrelimab combination therapy in locally advanced or metastatic NSCLC.12
The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.13
For more information, visit: View Source

About Lazertinib
Lazertinib is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. An analysis of the efficacy and safety of lazertinib from the Phase 3 study was published in The Journal of Clinical Oncology in 2023.14 In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

About Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.15,16 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.17 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.18 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.19,20,21,22,23 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.24 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.25,26

RYBREVANT IMPORTANT SAFETY INFORMATION3

WARNINGS AND PRECAUTIONS  

Infusion-Related Reactions
RYBREVANT can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. 

Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity. 

Interstitial Lung Disease/Pneumonitis
RYBREVANT can cause interstitial lung disease (ILD)/pneumonitis. Based on the safety population, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT due to ILD/pneumonitis.  

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Dermatologic Adverse Reactions
RYBREVANT can cause rash (including dermatitis acneiform), pruritus and dry skin. Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients.

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT. 

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen. Alcohol-free emollient cream is recommended for dry skin.

If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity
RYBREVANT can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity. 

Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the final dose of RYBREVANT.

Adverse Reactions
The most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).

Please read the full Prescribing Information for RYBREVANT.