On June 4, 2021 Candel Therapeutics, Inc., a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported initial results from an ongoing Phase 1 clinical trial of its oncolytic virus, CAN-3110, in patients with high-grade glioma (HGG) that has recurred after initial treatment (Press release, Candel Therapeutics, JUN 4, 2021, View Source [SID1234583579]). The data are presented today in an Oral Abstract Session of the Clinical Science Symposium at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"This is the first clinical trial of a novel oncolytic HSV engineered to selectively express ICP34.5 in tumor cells, leading to tumor-specific cell death. This novel oncolytic viral immunotherapy has been shown to be well tolerated with primarily low grade, and manageable side effects"

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Highlights from the Oral Abstract Session of the Clinical Science Symposium at ASCO (Free ASCO Whitepaper) 2021

An ongoing Phase 1 study is evaluating the safety and activity of CAN-3110, an engineered replication-competent herpes simplex virus (HSV) oncolytic viral immunotherapy, in patients with HGG who have experienced disease progression following prior treatment with standard of care therapies. As of the data cutoff date of April 21, 2021:

30 patients were evaluable for safety.
Nine dose levels ranging from 1×106 to 1×1010 plaque forming units (PFU) were administered.
No dose-limiting toxicity was observed. The maximum administered dose was 1×1010 PFU.
CAN-3110 was well-tolerated and all but one adverse events (AEs) were Grade 1 or 2.
A preliminary Kaplan-Meier estimate of median overall survival was 11.7 months.
All patients have been treated for more than 12 months.
One patient who responded for over a year, a 56-year-old male with multifocal glioblastoma, demonstrated a significant reduction in both an injected and an uninjected lesion, suggesting an abscopal effect of CAN-3110.
An additional 12 patients have been enrolled into a dose expansion arm of the trial.
"CAN-3110 has demonstrated a significant number of durable responses in patients with high-grade glioma who experienced disease progression following prior standard of care therapy," said Antonio Chiocca, MD, PhD, FAANS, Neurosurgeon-in-Chief and Chairman, Department of Neurosurgery at Brigham and Women’s Hospital. "The results of this first-in-human study are encouraging as they demonstrate a median overall survival that was substantially longer than the six to nine months typically observed for these patients as well as a favorable safety profile."

"This is the first clinical trial of a novel oncolytic HSV engineered to selectively express ICP34.5 in tumor cells, leading to tumor-specific cell death. This novel oncolytic viral immunotherapy has been shown to be well tolerated with primarily low grade, and manageable side effects," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel Therapeutics. "There are few treatment options for patients with high-grade glioma whose tumors progress following initial surgery and chemoradiation. We are encouraged by the duration of the responses observed to date in this patient population given the extremely limited treatment options. Based on these data, we are excited to advance this innovative agent into further clinical trials."

Details of the presentation are as follows:

Abstract Title: First-in-human CAN-3110 (ICP34.5 expressing HSV-1 oncolytic virus) in patients with recurrent high-grade glioma

Presenter: Dr. E. Antonio Chiocca

Session Date and Time: The presentation is available to ASCO (Free ASCO Whitepaper) attendees beginning June 4, 2021 at 9 AM EDT/ 6 AM PDT and has been reposted to the Candel Therapeutics website at www.candeltx.com/news

Abstract Link: View Source

Session Title: CNS Targeting: From Delivery to Biomarker Assessment

Abstract Number: 2009

About CAN-3110

CAN-3110 is an HSV replication-competent oncolytic virus engineered to enhance selective killing of malignant cells while sparing healthy normal neighboring cells. CAN-3110 selectively expresses ICP34.5, a key gene in HSV replication, in tumor cells that overexpress nestin, a cytoskeletal protein. Nestin is highly expressed in glioma cells and other tumor tissue but is absent in the healthy adult brain.

Candel is evaluating the effects of treatment with CAN-3110 for recurrent glioblastoma. For more information on this clinical study, please visit View Source

On June 4, 2021 InnoCare (HKEX: 09969), a leading biopharmaceutical company focusing on cancer and autoimmune diseases, reported the latest clinical data for the pan-FGFR inhibitor gunagratinib today at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, InnoCare Pharma, JUN 4, 2021, View Source [SID1234583597]). This is the first time InnoCare has presented gunagratinib’s clinical data at an international academic conference, showing good safety and tolerability.

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Updated Results from the Phase I Study of a highly selective irreversible FGFR inhibitor ICP-192 (gunagratinib) for patients with advanced solid tumors with abnormal FGFR gene

Abstract Number: 4092

ICP-192 (gunagratinib), developed by InnoCare Pharma, is a novel pan-FGFR (fibroblast growth factor receptors) inhibitor that potently and selectively inhibits FGFR activities irreversibly by covalent binding. Preclinical data showed that gunagratinib overcomes the acquired resistance to the first-generation reversible FGFR inhibitors.

Gunagratinib is currently in clinical phase I/II. The safety and tolerability as well as pharmacokinetics/pharmacodynamics (PK/PD) of gunagratinib were evaluated in patients with advanced solid tumors, and the preliminary anti-tumor activity was evaluated by RECIST1.1 in patients with FGF/FGFR gene aberrations.

As of February 2021, a total of 30 patients had received the treatment of gunagratinib. Gunagratinib performed well in safety and tolerance, the maximum tolerated dose (MTD) had not been reached. Among the 12 patients with FGF/FGFR gene aberrations who have completed at least one tumor assessment, the overall response rate (ORR) was 33.3%, including 1 patient (8.3%) of cholangiocarcinoma with complete response (CR) and 3 patients (25%) with partial response (PR), 7 patients achieved SD. The disease control rate (DCR) was 91.7%.

Professor Ye Guo, the Deputy Director of Oncology Medical Department of Shanghai Oriental Hospital and the Director of Clinical Center for PhaseⅠsaid, "Gunagratinib is safe and well-tolerated in patients with advanced solid tumors. Anti-tumor activity was demonstrated in patients with FGF/FGFR geneaberrations in multiple tumor types, including cholangiocarcinoma. Better response is expected with the increase of treatment durations."

The 2021 ASCO (Free ASCO Whitepaper) Annual Meeting will be held online from June 4th to 8th, 2021. The ASCO (Free ASCO Whitepaper) annual meeting is the most important and professional academic event in the global oncology field, which will showcase the international cutting-edge clinical oncology research results and tumor treatment technologies.

On June 4, 2021 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune disease, announces new interim data from its Phase II TACTI-002 study (also designated KEYNOTE-798) with a data cut-off date of 16 April 2021. The data will be presented in two poster presentations by Dr Tim Clay, Investigator, St John of God Subiaco Hospital, Perth, Australia and Dr Irene Brana, Investigator, Vall d’Hebron Institute of Oncology, Barcelona, Spain at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting in on-demand sessions available from 9 am on 4 June 2021, US Eastern Time at this year’s virtual conference. The posters will also be made available on Immutep’s website from that time at:

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View Source

TACTI-002 is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of Immutep’s lead product candidate eftilagimod alpha ("efti" or "IMP321") with MSD’s KEYTRUDA (pembrolizumab) in up to 183 patients with non-small cell lung cancer (NSCLC) in 1st and 2nd line (Parts A and B, respectively) or 2nd line head and neck squamous cell carcinoma (HNSCC, Part C).

Immutep CSO and CMO, Dr Frederic Triebel said: "As more and more industry focus is on LAG-3 therapies and it is in the spotlight of this year’s ASCO (Free ASCO Whitepaper), we are very pleased to be reporting such robust and exciting results from our TACTI-002 study of efti in combination with pembrolizumab. We are seeing nearly 50% of the evaluable 1st line NSCLC patients responding to the therapy, as scored by a blinded independent central review committee, with responses in all PD-L1 subgroups and a favourable median PFS. Overall, the NSCLC patients receiving this 1st line therapy are living 8.2 months without their disease progressing, a promising improvement for a chemo-free 1st line regimen. In effect, we are seeing an improvement in patient outcomes compared with that historically seen with anti-PD-1 monotherapy but with a similar safety profile and, also, comparable results in terms of ORR and PFS to chemo + anti-PD-1 combination therapy but, importantly, with a longer duration of response and lower toxicity."

Investigator, A/Prof Tim Clay, St John of God Subiaco Hospital, Perth, Australia said: "The median PFS of 8.2 months in 1st line NSCLC patients is very encouraging compared to historical studies where pembrolizumab has been given as monotherapy in comparable patient groups. There remains a great need for more effective chemotherapy free regimens in the treatment of NSCLC. These data are exciting and as a result, we will be expanding recruitment with 74 additional patients for Part A."

Investigator, Dr Irene Brana, Vall d’Hebron Institute of Oncology, Barcelona, Spain, said: "The sustained and durable responses reported in 2nd line HNSCC patients are improving as TACTI-002 progresses, with about 14% of patients now benefiting from a complete disappearance of all their tumour lesions. Responses are particularly good in PD-L1 expressing patients (CPS ≥ 1) where an ORR of 45.8% is reported. The strength of these results validates the decision to explore the combination of efti and pembrolizumab in a new Phase IIb study, TACTI-003 in 1st line HNSCC patients which is starting in the coming months."

Table 1 – TACTI-002 Interim ORR Results for Part A and C (data cut-off date: 16 April 2021)

Part A
1st line NSCLC1 Part C
2nd line HNSCC2
Tumour Response
Best Overall Response (BOR) per iRECIST Stages 1 & 2
N (%)
Total N=36 Stage 1 & 2
N (%)
Total N=37
Complete Response (CR) 2 (5.6) 5 (13.5)
Partial Response (PR) 13 (36.1) 6 (16.2)
Stable Disease (SD) 10 (27.8) 3 (8.1)
Progressive Disease (PD) 6 (16.7) 17 (45.9)
Not Evaluable 5 (13.9) 6 (16.2)
Disease Control Rate (DCR) 25 (69.4) 14 (37.8)
Objective Response Rate (ORR) 15 (41.7) 11 (29.7)
ORR in evaluable pts 15 (48.4), N=31 11 (35.5), N=31
Key Findings

1st line NSCLC – Part A

Sustained and durable responses: 15 patients with responses giving an ORR of 41.7% on an intention-to-treat basis and 48.4% in evaluable patients, as assessed by blinded independent committee read
None of the patients with a confirmed response progressed within 6 months and the median duration of response (DoR) is currently estimated to be more than 13 months in patients unselected for PD-L1 expression
2/36 (5.6%) patients had a Complete Response (complete disappearance of tumour lesions) and 23/36 (63.9%) of patients had a target lesion decrease (includes the 2 CRs)
Durable responses observed in all PD-L1 subgroups as assessed by local investigator read,3 for example:
ORR in the ≥ 1% PD-L1 subgroup was 44.0% (11/25)
ORR in the < 50% PD-L1 subgroup was 31.6% (6/19)
ORR in the ≥ 50% PD-L1 subgroup was 53.8% (7/13)
Median overall PFS is 8.2 months in patients unselected for PD-L1 expression, as assessed by local investigator read. This is very promising for a chemo-free 1st line regimen. Median PFS increases to 11.8 months in the ≥ 50% PD-L1 subgroup and median PFS in the < 1% PD-L1 subgroup is 4.1 months
Conclusion: The data presented for 1st line NSCLC is very encouraging and will be broadened by the ongoing recruitment in this patient population to form a solid basis for late-stage clinical development.

2nd line HNSCC – Part C

11 patients with responses giving an ORR of 29.7% on an intention-to-treat basis and 35.5% in evaluable patients
Durable responses with now 5 patients (13.5%) having a Complete Response. So far median duration of response is not yet reached. None of the patients with a response progressed within 6 months
In patients unselected for PD-L1 expression, median PFS is 2.1 months and median OS is 12.6 months
In patients in PD-L1 CPS ≥ 1 subgroup (N=24), ORR is 45.8%, median PFS is 4.1 months, and median OS is 12.6 months
Conclusion: The 2nd line HNSCC data is mature and continues to be very encouraging and forms an excellent basis to move into the 1st line HNSCC indication via Immutep’s randomised Phase IIb TACTI-003 study which is expected to start in mid-2021.

2nd line NSCLC – Part B
Stage 1 results were reported in November 2020 at SITC (Free SITC Whitepaper) and Overall Survival is trending favourably. Stage 2 recently opened for patient enrolment and combined results from Stages 1 & 2 are expected to be reported later this year.

Safety
The combination treatment continues to be safe and well tolerated with no new safety signals reported thus far.

Recruitment Update
Trial recruitment continues to progress well, with 127 patients out of up to 183 already participating at 12 clinical sites across Australia, Europe, the UK and US. At present, recruitment is ongoing for the expansion stage of Part A and Stage 2 of Part B.

Recruitment details for each Part of the trial are shown below and are current as at 1 June 2021.

Table 2 – TACTI-002 Recruitment (as at 1 June 2021)

Stage 1 (N)
Actual / Target Stage 2 (N)
Actual / Target Recruitment
Status Expansion Stage
Actual / Target
Part A (1st line NSCLC) 17/17 19/19 EXPANDED 23/74
Part B (2nd line NSCLC) 23/23 6/13 RECRUITING
Part C (2nd line HNSCC) 18/18 21/194 COMPLETE
Next Results
Immutep currently expects to report further interim data from Part A, final data from Part C, and new results from Stages 1 & 2 of Part B in 2H calendar year 2021 or early calendar year 2022.

Webcast Details
Immutep will present this data in a global webcast for investors. Details are as follows:

Date & Time:

Thursday, 10 June 2021, at 7:00 am Australian Eastern Daylight Time (AEDT) (Wednesday, 9 June, at 5:00 p.m. U.S. ET)

Register:

View Source

Questions:

Investors are invited to submit questions in advance via [email protected].

A replay of the webcast will also be available at www.immutep.com from the day after the event.

About the TACT-002 Trial
TACTI-002 (Two ACTive Immunotherapies) is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of efti with MSD’s KEYTRUDA (pembrolizumab) in up to 183 patients with second line head and neck squamous cell carcinoma or non-small cell lung cancer in first and second line.

The trial is a Phase II, Simon’s two-stage, non-comparative, open-label, single-arm, multicentre clinical study that is taking place in study centres across Australia, Europe, the UK and US.

Patients participate in one of the following:
• Part A – First line Non-Small Cell Lung Cancer (NSCLC), PD-X naive
• Part B – Second line NSCLC, PD-X refractory
• Part C – Second line Head and Neck Squamous Cell Carcinoma (HNSCC), PD-X naive

TACTI-002 is an all-comer study in terms of PD-L1 status, a well-known predictive marker for response to pembrolizumab monotherapy especially in NSCLC and HNSCC. PD-L1 expression is typically reported in three groups for NSCLC: < 1%, 1-49% and ≥ 50% (Tumour Proportion Score or TPS) and in HNSCC: < 1, 1-19 and ≥ 20 (Combined Positive Score or CPS). Patients with a high PD-L1 status are typically more responsive to anti-PD-1 therapy such as pembrolizumab, whereas those with low PD-L1 status are overall significantly less responsive.

On June 4, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported data from TG-1701, the Company’s investigational once-daily, oral BTK inhibitor, as a monotherapy and as a triple therapy in combination with ublituximab, the Company’s novel glycoengineered anti-CD20 monoclonal antibody, and UKONIQ (umbralisib), the Company’s once-daily, inhibitor of PI3K-delta and CK1-epsilon in patients with front line or relapsed/refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, JUN 4, 2021, View Source [SID1234583532]). Data from this trial were made available on demand this morning during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Presentation highlights are included below.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are pleased to see that with additional patients and longer follow-up, TG-1701, our BTK inhibitor, continues to show encouraging clinical activity paired with what appears to be a tolerable safety profile, especially in the triple combination with U2. It is also exciting to see some early complete responses in patients treated with the triple therapy. We look forward to continuing to enroll on this trial and presenting additional data."

PRESENTATION HIGHLIGHTS:

Poster Presentation Title: TG-1701, A Selective Bruton Tyrosine Kinase (BTK) Inhibitor, as Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Chronic Lymphocytic Leukemia (CLL) and Lymphoma

A total of 125 patients with R/R CLL or B-cell lymphoma have been treated with TG-1701, with patients receiving monotherapy in the dose-escalation cohort (n=25), 200 mg in a dose-expansion cohort (n=61), 300 mg in a CLL dose-expansion cohort (n=20), or TG-1701 in combination with U2 in the dose escalation cohort (n=19).
TG-1701 monotherapy was well tolerated and the maximum tolerated dose was not reached up to 400 mg QD.
Adverse Events (AEs) of special interest in patients treated with 200 mg and 300 mg QD of TG-1701 (n=81), included Grade 3 hypertension (4.9%), atrial fibrillation (1.2%), and no instances of major bleeding observed. Grade 3 AEs occurring in ≥10% of patients treated with U2+1701 included diarrhea (11%), neutropenia (11%), ALT increase (16%), and AST increase (16%), and Grade 4 AEs occurring in ≥10% of patients treated with U2+1701 included neutropenia (11%).
At a median follow up of 12.2 months in the 200 mg QD monotherapy expansion cohorts, overall response rates (ORR) were: 95% (19/20) in CLL, 65% (13/20) in mantle cell lymphoma (MCL), and 95% (19/20) in Waldenstrom macroglobulinemia (WM).
100% ORR observed at a median follow up of 8.6 months in the 300 mg CLL monotherapy cohort (n=19).
At a median follow up of 15.6 months, the 1701+U2 dose escalation (using doses of 100mg to 300 mg QD of TG-1701) resulted in 79% ORR, with 21% CR rate across patients with WM, CLL, marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (n=19).
Data presented at ASCO (Free ASCO Whitepaper) 2021 is available on the Publications page of the Company’s website at View Source

On June 4, 2021 Amgen (NASDAQ: AMGN) reported data on overall survival, a secondary endpoint, from the Phase 2 results of the CodeBreaK 100 clinical study for LUMAKRASTM (sotorasib) in previously treated patients with non-small cell lung cancer (NSCLC) during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. These data were also simultaneously published in the New England Journal of Medicine (NEJM). The publication includes mature overall survival and duration of response data, and results from subgroup and exploratory biomarker analyses.

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LUMAKRAS shows a median overall survival (OS) of 12.5 months among 124 evaluable patients, the majority of which were previously treated with both platinum-based chemotherapy and immunotherapy (81%) (data cutoff of March 15, 2021). The results confirmed an objective response rate (ORR) of 37.1%, duration of response (DoR) of 11.1 months and disease control rate (DCR) of 80.6%, with an additional patient achieving complete response (bringing the total to four complete responses and 42 partial responses) compared to previously reported results. The data published in NEJM are updated from results presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) held in January 2021 and are based on a longer follow-up time of 15.3 months.

"Patients with KRAS G12C-mutated non-small cell lung cancer face poor outcomes so we are pleased with these overall survival results and the impact LUMAKRAS may have for patients with this devastating mutation," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The results published in the New England Journal of Medicine further confirm the deep and durable responses we have seen with LUMAKRAS throughout the CodeBreaK clinical trial program, the most advanced KRAS G12C clinical trial program with the longest follow-up."

In exploratory analyses, tumor response to LUMAKRAS was consistently observed across a range of biomarker subgroups, including patient subgroups stratified by baseline PD-L1 expression levels and those with STK11 mutation. In the patient subsets separated by baseline PD-L1 expression (n=86), response and tumor shrinkage were observed across the range of baseline PD-L1 expression levels, with the response rate of 48% for the PD-L1 negative group (TPS <1%). Improved efficacy with LUMAKRAS was seen in STK11-mutant group with concurrent wild-type KEAP1 (n=22) with median progression free survival (PFS) of 11.0 months and median OS of 15.3 months.

"Sotorasib is the first KRASG12C inhibitor to show an overall survival benefit, and the data represent a major step forward for patients with KRAS G12C-mutated non-small cell lung cancer where standard of care options are suboptimal," said lead author Ferdinandos Skoulidis, M.D., Ph.D., assistant professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "KRAS has been one of the most challenging therapeutic targets in cancer research, and these practice-changing results give hope to patients with the KRAS G12C mutation who previously had no targeted treatment options."

LUMAKRAS received approval from the U.S. FDA on May 28, 2021, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. LUMAKRAS has received accelerated approval based on ORR and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Skoulidis reports research support from Amgen Inc.

About LUMAKRASTM (sotorasib)
Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS, a KRASG12C inhibitor.1 LUMAKRAS was the first KRASG12C inhibitor to enter the clinic and is being studied in the largest clinical program exploring more than 10 combinations with global investigator sites spanning five continents.

LUMAKRAS 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. As part of the evaluation for this accelerated approval, FDA is requiring a post-marketing trial to investigate whether a lower dose will have a similar clinical effect.

LUMAKRAS is also being studied in multiple other solid tumors.1

LUMAKRAS was granted Breakthrough Therapy designation in the U.S. and China. In the U.S., LUMAKRAS was reviewed by the FDA under its Real-Time Oncology Review (RTOR), a pilot program that aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Amgen is participating in the FDA’s Project Orbis initiative and through the initiative, has submitted Marketing Authorization Applications (MAAs) for sotorasib in Australia, Brazil, Canada and the United Kingdom. Additionally, Amgen has submitted an MAA in the EU and New Drug Applications in Japan (J-NDA), Switzerland, South Korea and United Arab Emirates.

LUMAKRASTM (sotorasib) U.S. Indication
LUMAKRASTM 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 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.
Please see LUMAKRASTM full Prescribing Information.

About Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.2 Overall survival rates for NSCLC are improving, but remain poor for patients with advanced disease and 5-year survival is only 7% for those with metastatic disease.3

KRAS G12C is the most common KRAS mutation in NSCLC.4 In the U.S., about 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation.5 Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with current therapies are suboptimal with a median progression-free survival of approximately 4 months following second-line treatment of KRAS G12C-mutated NSCLC.6 (Press release, Amgen, JUN 4, 2021, View Source [SID1234583549])