On January 20, 2022 AVEO Oncology (Nasdaq: AVEO), a commercial stage, oncology-focused biopharmaceutical company, reported that new efficacy and safety data from the first line (cohort A) of the phase 1b/2 DEDUCTIVE study of FOTIVDA (tivozanib) in combination with IMFINZI (durvalumab) in previously untreated metastatic hepatocellular carcinoma (HCC) are being presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (ASCO GI) Cancers Symposium (Press release, AVEO, JAN 20, 2022, View Source [SID1234605615]). In addition, two trials in progress posters are being presented, which showcases cohort B of the DEDUCTIVE HCC study that is currently enrolling HCC patients following prior bevacizumab and atezolizumab; and the Company, in collaboration with the University of Florida Health Cancer Center, is presenting the study design for the Phase 1b/2 IMMCO-1 trial of atezolizumab plus tivozanib in immunologically cold pancreatic, gallbladder and biliary cancers.

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"We believe that the safety and efficacy data observed in cohort A of the Phase 2 portion of the DEDUCTIVE study continue to support the development of tivozanib to serve as an attractive VEGFR TKI to use in combination with durvalumab in first line HCC patients," said Michael Bailey, President and Chief Executive Officer of AVEO. "The poster presentations at this year’s ASCO (Free ASCO Whitepaper) GI conference reflect the expanding scope of our pipeline as we leverage the potential efficacy of our lead program tivozanib through a combination strategy targeting a number of cancers."

Topline Efficacy and Safety Data Poster Title: A Phase 1b/2 Study of Tivozanib in Combination with Durvalumab in Subjects with Advanced Hepatocellular Carcinoma (DEDUCTIVE): Efficacy Results in Previously Untreated Patients (Abstract #462 / Poster: M10)

The Company will present topline data for cohort A of the DEDUCTIVE study, which is assessing the safety and efficacy of tivozanib in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with unresectable locally advanced or metastatic, previously untreated HCC. A total of 20 patients with advanced or metastatic HCC were enrolled in cohort A of the Phase 2 portion of the study safety and efficacy of tivozanib plus durvalumab. Patients received 0.89 mg of tivozanib orally once daily for 21 days followed by seven days off therapy in combination with 1500 mg of durvalumab intravenously (IV) on day one given every four weeks, on a 28 day cycle. The combination was well tolerated, with three patients showing Grade 3 TRAEs, and no Grade 4 TRAEs or treatment-related deaths. The combination demonstrated a 27.8% partial response (PR) rate and disease control rate (PR + stable disease) 67.8%, with a median PFS of 7.3 months and a 1-year OS of 76%, which positions the tivozanib combination well relative to other VEGF ICI combinations in the setting.

Trials in Progress Poster Presentation titled: A Phase 1b/2 Open Label Study of Tivozanib in Combination with Durvalumab in Subjects with Advanced Hepatocellular Carcinoma: DEDUCTIVE – (Abstract: TPS499 / Poster: Online Only)

The DEDUCTIVE study is a multicenter, open-label study to evaluate the safety, tolerability, and efficacy of tivozanib in combination with durvalumab in subjects with advanced HCC previously untreated (cohort A) or bevacizumab- and atezolizumab-pretreated HCC (cohort B). Cohort A is fully enrolled and cohort B will enroll up to 20 subjects. Cohort A showed a promising safety and efficacy profile in previously untreated patients and cohort B has the potential demonstrate the first clinical study results in the emerging population of prior bevacizumab and atezolizumab treated patients.

The rationale for a combination therapy of tivozanib plus durvalumab to treat HCC draws on the potential synergistic mechanisms of tivozanib and durvalumab to remove inhibition of the immune response that mediates antitumor activity. The selectivity and favorable tolerability of the VEGFR TKI tivozanib may allow it to be used as a combination therapy with an immune checkpoint inhibitor, such as durvalumab.

The DEDUCTIVE trial is being conducted as part of a clinical collaboration between AVEO and AstraZeneca. AVEO is serving as the study sponsor.

Trials in Progress Poster Presentation titled: A phase 1b/2 study (IMMCO-1) of atezolizumab plus tivozanib in immunologically cold pancreatic, gallbladder, and biliary cancers – (Abstract: TPS491 / Poster: N8)

The ongoing IMMCO-1 study is an open-label, non-randomized Phase 1b/2 signal seeking basket study of the combination of the tivozanib and atezolizumab in multiple immunologically cold tumors, including pancreatic, gallbladder and biliary cancers. The co-primary endpoints are safety and efficacy. The Phase 1b portion will assess the safety profile of the combination of tivozanib and atezolizumab with a potential dose de-escalation of tivozanib using a 3+3 study design to yield a recommended Phase 2 dose.

VEGF is thought to play a key role in modulating the anti-tumor immune response. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade. Combined use of a VEGF tyrosine kinase inhibitor (TKI) and checkpoint inhibitor is already standard of care in advanced kidney, cervical and endometrial cancers. There has been suggestion that such a combination may have clinical activity in some microsatellite stable (MSS) GI malignancies.

The Phase 2 portion is expected to enroll up to 26 additional patients using the recommended Phase 2 dose using the Simon two-stage design of recruitment. This signal seeking study is looking to confirm the best objective response rate for evaluable patients increasing from < 7% (null hypothesis) to 25% (one-sided alpha = 0.05; 80% power).

The three posters to be presented at the 2022 ASCO (Free ASCO Whitepaper) GI Cancers Symposium are available on the Publications page of the AVEO Oncology website (click here). Details on the presentation are available on the 2022 ASCO (Free ASCO Whitepaper) GI website (click here).

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.2 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.3 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,4 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On January 20, 2022, Apellis Pharmaceuticals, Inc., a Delaware corporation (the "Company"), entered into an Open Market Sale AgreementSM (the "Agreement") with Jefferies LLC, as agent ("Jefferies"), pursuant to which the Company may offer and sell shares of its common stock, $0.0001 par value per share (the "Shares"), from time to time through Jefferies (the "Offering") (Filing, 8-K, Apellis Pharmaceuticals, JAN 20, 2022, View Source [SID1234605614]). The Company has also filed a prospectus supplement with the Securities and Exchange Commission (the "SEC") in connection with the Offering (the "Prospectus Supplement") under the Company’s existing automatic shelf Registration Statement on Form S-3 (File No. 333-235830), which became effective on January 7, 2020 (the "Registration Statement"). Pursuant to the Prospectus Supplement, the Company may offer and sell Shares having an aggregate offering price of up to $300.0 million.

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Upon delivery of a placement notice and subject to the terms and conditions of the Agreement, Jefferies may sell the Shares at market prices by any method deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the "Securities Act"), including sales made directly on or through The Nasdaq Global Select Market ("Nasdaq"), the existing trading market for the Company’s common stock.

The Company or Jefferies may suspend or terminate the offering of Shares upon notice to the other party, subject to certain conditions. Jefferies will act as sales agent on a commercially reasonable efforts basis consistent with its normal trading and sales practices and applicable state and federal law, rules and regulations and the rules of Nasdaq.

The Company has agreed to pay Jefferies commissions for its services of acting as agent of up to 3.0% of the gross proceeds from the sale of the Shares pursuant to the Agreement. The Company has also agreed to provide Jefferies with customary indemnification and contribution rights.

A copy of the Agreement is attached as Exhibit 1.1 hereto and is incorporated herein by reference. The foregoing description of the material terms of the Agreement is qualified in its entirety by reference to such exhibit.

Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Company, has issued a legal opinion relating to the Shares. A copy of such legal opinion, including the consent included therein, is attached as Exhibit 5.1 hereto.

The Shares will be sold pursuant to the Registration Statement, and offerings of the Shares will be made only by means of the Prospectus Supplement. This Current Report on Form 8-K shall not constitute an offer to sell or solicitation of an offer to buy the Shares, nor shall there be any sale of the Shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities law of such state or jurisdiction.

Item 1.02
Termination of a Material Definitive Agreement.

In connection with the entry into the Agreement on January 19, 2022, the Company terminated its prior amended and restated equity distribution agreement, dated as of October 4, 2019, by and among the Company, Citigroup Global Markets Inc. ("Citigroup") and Jefferies (the "Prior Agreement"), in accordance with its terms. The Prior Agreement provided for Citigroup and Jefferies to sell shares of common stock having an aggregate offering price of up to $150.0 million by any method deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act. The Company cannot make any further sales of its common stock pursuant to the Prior Agreement.

On January 20, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that Walter V. Klemp, Founder, President, CEO and Chairman, will participate in the Virtual Investor 2022 Top Picks Conference on Thursday, January 27, 2022 at 9:00 AM ET (Press release, Moleculin, JAN 20, 2022, View Source [SID1234605611]).

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Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors. (PRNewsfoto/Moleculin Biotech, Inc.)

As part of the virtual event, the Company will provide a corporate presentation, followed by a moderated interactive Q&A session. In addition to the moderated portion of the event, all investors and interested parties will have the opportunity to submit questions live during the event. Interested parties may also pre-submit questions in advance of the live event, which can be sent via the conference website at virtualinvestorco.com. The Company will answer as many questions as possible during the event.

A live video webcast of the presentation will be available on the Events page of the Investors section of the Company’s website (moleculin.com). A webcast replay will be available two hours following the live presentation and will be accessible for one year.

On January 20, 2022 IntegraGen and BIOASTER reported they have been collaborating for several years in the context of genomic and transcriptomic analyses (Press release, Integragen, JAN 20, 2022, View Source [SID1234605609]). Driven by a desire to strengthen this relationship further, the two entities have entered into a long-term partnership agreement (Master Research Service Agreement). This agreement will facilitate and accelerate exchanges between the two teams, and thus offer integrated, streamlined and efficient solutions aimed at healthcare industries in France.

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Created in 2012 from an initiative by the French Technological Research Institute (IRT), BIOASTER is a non-profit foundation with a unique and innovative technological model to meet new challenges related to microbiology and infectious diseases. Its objective is to connect academia and businesses in order to develop and carry out collaborative research projects which have a high impact on patients.

In pursuit of its objectives, BIOASTER seeks to rely on its reference partners, who are leaders in their field. As such, the IRT is able to provide an integrated technological offer adapted to the needs of its research projects, both in terms of variety and volume.

"IntegraGen has demonstrated its ability to respond quickly to our sequencing needs and to provide us with quality data in a timely manner. Here at BIOASTER, we are delighted to strengthen our collaboration with an expert team in whom we have total confidence," says Adrien Saliou, B.Eng, PhD, Genomics and Transcriptomics Team Leader, OMICS Hub, BIOASTER.

"Our collaboration with BIOASTER is based on the responsiveness, communication and professionalism of the teams at both our institutions. It is an honour for IntegraGen to be asked to contribute to the challenge of understanding the mechanisms of biological systems and the fight against infectious agents while working alongside a key player in the field of microbiology," Emmanuel Martin, Chief Operating Officer of the OncoDNA Group.

On January 20, 2022 Amgen (NASDAQ: AMGN) reported that LUMAKRAS (sotorasib) has been approved in Japan for the treatment of KRAS G12C-mutated positive, unresectable, advanced and/or recurrent non-small cell lung cancer (NSCLC) that has progressed after systemic anticancer therapy (Press release, Amgen, JAN 20, 2022, View Source [SID1234605607]).

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"Today’s approval of LUMAKRAS as the first and only KRASG12C inhibitor marks a paradigm shift in the treatment of patients with non-small cell lung cancer in Japan," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "In just over three years since the first patient was dosed in the pivotal CodeBreaK 100 trial, LUMAKRAS is now approved in nearly 40 countries, illustrating our commitment to accelerating transformative medicines for patients living with cancers that have yet to be fully addressed."

The approval by the Japan Ministry of Health, Labour and Welfare (MHLW) is based on positive results from the Phase 2 CodeBreaK 100 clinical trial in NSCLC, the largest trial conducted to date for patients with the KRAS G12C mutation. Based on the approved label in Japan, LUMAKRAS 960 mg, orally administered once-daily, demonstrated an objective response rate (ORR) of 37% (95% CI: 28.8-46.6) in 123 evaluable patients (including 10 Japanese patients* with a data cutoff date: Sept. 1, 2020). Adverse reactions were observed in 128 (67%) of 190 patients† (including 13 Japanese patients). The most common adverse reactions (incidence ≥ 5%) were diarrhea (28%), nausea, increased alanine aminotransferase (ALT) and increased aspartate aminotransferase (AST) (16% each), fatigue (11%), increased blood alkaline phosphatase (8%), vomiting (7%) and abdominal pain (5%).

Results from the Phase 2 CodeBreaK clinical trial in NSCLC were published in The New England Journal of Medicine.

"KRAS gene mutations are one of the oldest known cancer driver gene mutations," said Steve Sugino, president and representative director, Amgen K.K. "However, it has proven to be very difficult to develop drugs for the treatment of KRAS gene mutations. For nearly 40 years, researchers have said that the mutation was ‘undruggable.’ I am very pleased that LUMAKRAS is now approved as a new treatment option for patients in Japan."

"The prognosis for patients with non-small cell lung cancer who have distant metastases or whose disease has relapsed after surgery, is generally poor," said Tetsuya Mitsudomi, M.D., professor, Department of Surgery, Division of Thoracic Surgery at Kindai University School of Medicine, past-president of the International Association for the Study of Lung Cancer (IASLC) and past-president of the Japan Lung Cancer Society (JLCS). "Recent developments in molecular-targeted drugs and immunotherapy have dramatically improved the prognosis for these patients. However, despite the relatively high frequency of the KRAS G12C mutation, no drugs specifically targeting this mutation have been available until recently. Therefore, the approval of LUMAKRAS in Japan is a major milestone in the treatment of non-small cell lung cancer patients with KRAS G12C mutations."

On March 11, 2021, the MHLW designated sotorasib as an orphan drug.

*3 subjects (including 1 Japanese subject) without measurable lesions at baseline as determined by the central review were excluded.
†Patients with non-small cell lung cancer who received at least 1 dose of this drug 960 mg in the phase I and II parts.

About LUMAKRAS/LUMYKRAS (sotorasib)
Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.1 LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.2

Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, including triplets, with clinical trial sites spanning five continents. To date, over 4,000 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use.

In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval anywhere in the world with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the United Arab Emirates, the European Union and Switzerland, and in Canada and Great Britain under the FDA’s Project Orbis. Through Project Orbis, Amgen also has Marketing Authorization Applications (MAAs) for sotorasib in review in Australia, Brazil, Singapore and Israel. Additionally, Amgen has submitted MAAs in South Korea, Turkey, Taiwan, Colombia, Thailand, Mexico, Hong Kong, Saudi Arabia, Argentina, Kuwait and Qatar.

LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.3

About Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the second most prevalent cancer in the world, and the total number of patients in Japan is estimated to be about 169,000.4,5 Lung cancer is also the leading cause of cancer site-specific mortality worldwide and in Japan, with an estimated 82,300 deaths annually.5 About 85-90% of lung cancer patients are classified as having NSCLC (such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma).6 NSCLC is a life-threatening, serious disease, and the 5-year survival rate of patients with stage IV NSCLC in Japan is 10.8% for adenocarcinoma and 2.7% for squamous cell carcinoma, indicating that the prognosis of this disease is still poor.7

KRAS G12C is the most common KRAS mutation in NSCLC.8 KRAS G12C mutation is reported to be found in approximately 13% of lung adenocarcinoma in the U.S. and 4.5% of non-squamous cell carcinoma in Japan.9,10 There is a significant unmet need as there are limited treatment options for patients with NSCLC harboring KRAS G12C mutations who have failed or lost response to first-line treatment. Outcomes with available therapies have been suboptimal, with median progression-free survival after second-line therapy reported to be approximately 4 months in patients with NSCLC harboring KRAS G12C mutations.11

About CodeBreaK
The CodeBreaK clinical development program for Amgen’s drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.2,3 Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.2 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been published.11

CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally-advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment. A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).

For information, please visit www.hcp.codebreaktrials.com.

Important Japan Product information

Product Name:

LUMAKRAS TABLETS 120 mg

Generic Name:

sotorasib

Indication:

KRAS G12C mutated, unresectable, advanced and/or recurrent non-small cell lung cancer that has progressed after systemic anticancer therapy

Precautions related to indications:

The product should be administered to patients who are confirmed as KRAS G12C-mutated by a pathologist with adequate experience or by testing at a testing facility. Approved in vitro diagnostics should be used for the testing. List of the approved in vitro diagnostics is available on the following website.
View Source
Physicians should select patients to be treated with the product based on their good understanding of the "17. Clinical Studies" section of the package insert, and of the efficacy and safety of the product, with careful consideration of the use of therapies other than the product.
The efficacy and safety of the product in the first-line therapy have not been established.
The efficacy and safety of the product in postoperative adjuvant therapy have not been established.
Dosage and Administration:

The usual adult dosage is 960 mg of sotorasib administered orally once daily. The dose may be reduced according to the patient’s condition.

Please refer to the latest package insert for details.

LUMAKRAS (sotorasib) U.S. Indication

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS (sotorasib) Important U.S. Safety Information

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions

The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions

Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.