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- | Lumakras (sotorasib) / Amgen
Journal: Sotorasib in KRAS-Mutated Colorectal Cancer. (Pubmed Central) - Jul 10, 2024
No abstract available
- || Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Review, Journal: Assessment of KRASG12C inhibitors for colorectal cancer. (Pubmed Central) - Jul 9, 2024
This review provides an update on clinical trials involving CRC patients treated with KRASG12C inhibitors as a monotherapy or combined with other drugs. Mechanisms that contribute to resistance to KRASG12C inhibitors and the development of novel RAS inhibitors with potential to escape such mechanisms of resistance are also discussed.
- | Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen, RMC-7977 / Revolution Medicines
Journal: Mechanisms of response and tolerance to active RAS inhibition in KRAS-mutant NSCLC. (Pubmed Central) - Jul 8, 2024
In patients with advanced KRASG12C-mutant NSCLC, the presence of mucinous histological features portended poor response to sotorasib or adagrasib. Our results have potential implications for personalized medicine and the development of rational RAS inhibitor-anchored therapeutic strategies.
- | Krazati (adagrasib) / BMS, MRTX1133 / BMS, Lumakras (sotorasib) / Amgen
Journal: Mechanisms of resistance to oncogenic KRAS inhibition in pancreatic cancer. (Pubmed Central) - Jul 8, 2024
In PDAC cell lines and organoid models treated with the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition and PI3K-AKT-mTOR signaling associate with resistance to therapy...Combination treatment with KRASG12D inhibition and chemotherapy significantly improved tumor control in PDAC mouse models. Collectively, these data elucidate co-evolving resistance mechanisms to KRAS inhibition and support multiple combination therapy strategies.
- | Lumakras (sotorasib) / Amgen
Journal, Circulating tumor DNA, Metastases: Clinical utility of circulating tumor DNA in patients with advanced KRASG12C-mutated non-small cell lung cancer treated with sotorasib. (Pubmed Central) - Jul 7, 2024
P=N/A
We identified KRAS amplifications as a potential recurring resistance mechanism to sotorasib. Identifying patients with superior prognosis could aid in optimizing time of treatment initiation, and identifying patients at risk of early progression could allow for earlier treatment decisions.
- | Lumakras (sotorasib) / Amgen
Trial completion date, Metastases: AMG 510 Ethnic Sensitivity Study (CodeBreaK 105). (clinicaltrials.gov) - Jul 5, 2024
P1, N=12, Active, not recruiting, Sponsor: Amgen
Identifying patients with superior prognosis could aid in optimizing time of treatment initiation, and identifying patients at risk of early progression could allow for earlier treatment decisions. Trial completion date: Jul 2024 --> Dec 2024
- || Lumakras (sotorasib) / Amgen
PK/PD data, Journal: Effect of Strong CYP3A4 Inhibition, CYP3A4 Induction, and OATP1B1/3 Inhibition on the Pharmacokinetics of a Single Oral Dose of Sotorasib. (Pubmed Central) - Jul 3, 2024
Trial completion date: Jul 2024 --> Dec 2024 The impact of CYP3A4 inhibition was interrogated utilizing repeat doses of 200
- || Lumakras (sotorasib) / Amgen
Clinical, Journal, HEOR, Cost-effectiveness, Cost effectiveness: Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRASG12C mutation in China and the United States. (Pubmed Central) - Jul 1, 2024
Sotorasib had a cost effect from the perspective in the United States. However, sotorasib had no cost effect from the perspective in China, and only when the WTP exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.
- || Lumakras (sotorasib) / Amgen
Review, Journal: Sotorasib as Fourth-Line Treatment in Pancreatic Cancer: A Case Report and Literature Review. (Pubmed Central) - Jun 25, 2024
Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
- Krazati (adagrasib) / BMS, Pozenveo (poziotinib) / Assertio, Lumakras (sotorasib) / Amgen
Pan-HER Inhibition Overcomes Feedback Adaptation Resistance to KRAS G12C Inhibition in KRAS G12C Mutant Non-Small Cell Lung Cancer (Grace Murray Hopper Auditorium, Yale West Campus Conference Center) - Jun 23, 2024 - Abstract #LUNGSPORE2024LUNG_SPORE_66;
KRAS G12C inhibitors sotorasib and adagrasib are FDA approved for advanced/metastatic KRAS G12C-positive NSCLC, although the duration of benefit from these drugs is relatively modest and therapeutic resistance typically emerges relatively quickly to these drugs...We observed that in combination with KRAS G12C inhibitors pan-HER TKIs such as poziotinib yielded a synergistic effect compared to HER2 TKI treatment...The combination of pan-HER TKIs with KRAS G12C inhibitor suppressed tumor growth significantly as compared to KRAS G12C inhibitor alone with a tolerable toxicity profile in KRAS G12C mutant patients derived xenograft models. Collectively, our findings indicate that the adaptive feedback activation of HER family members, including not only EGFR but also HER2 and HER3, diminishes the efficacy of KRAS G12C inhibitors against KRAS G12C-positive NSCLC tumor cells, and that the combination of pan-HER TKIs with KRAS G12C inhibitors may be more effective than KRAS G12C inhibitors alone.
- Identifying Resistant Mechanisms To Direct KRAS-Inhibitors (Grace Murray Hopper Auditorium, Yale West Campus Conference Center) - Jun 23, 2024 - Abstract #LUNGSPORE2024LUNG_SPORE_28;
The identification of selective inhibitors of other oncogenic KRAS alleles, such as the noncovalent KRAS-G12D inhibitor, MRTX1133, and a pan-KRAS-inhibitor drug, BI3706674 is also a promising next step in the treatment of KRAS-dependent malignancies...We are currently performing in vitro and In vivo studies to understand the therapeutic efficacy of a TEAD inhibitor (VT107) in combination with KRASi (MRTX849 or MRTX1133) to either reverse or prevent resistance to the direct KRAS inhibitors. Successful completion of this research will help address the urgent need to understand ways to overcome resistance to KRAS inhibitors and increase their clinical efficacy.
- || Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Review, Journal, IO biomarker: Targeting KRASG12C in Non-Small-Cell Lung Cancer: Current Standards and Developments. (Pubmed Central) - Jun 20, 2024
New KRASG12C inhibitors and several combination therapy strategies, including with immune checkpoint inhibitors, are being studied in clinical trials. The aim of this review is to explore the clinical impact of KRAS, and outline different treatment approaches, focusing on the novel treatment of KRASG12C-mutated NSCLC.
- | azenosertib (ZN-c3) / Zentalis Pharma, Lumakras (sotorasib) / Amgen
Journal: Targeting WEE1 enhances the antitumor effect of KRAS-mutated non-small cell lung cancer harboring TP53 mutations. (Pubmed Central) - Jun 19, 2024
Notably, the combined inhibition of KRAS-G12C and WEE1 consistently suppresses tumor growth. Our results suggest targeting WEE1 as a promising therapeutic strategy for KRAS-mutated NSCLC with TP53 mutations.
- || MRTX1133 / BMS, Lumakras (sotorasib) / Amgen
Review, Journal: Inhibition of GTPase KRASG12D: a review of patent literature. (Pubmed Central) - Jun 17, 2024
It is important to note, however, that understanding the mechanisms of acquired resistance caused by KRAS inhibition and developing additional combination therapies is crucial. Moreover, seeking covalent inhibition of KRASG12D also holds significant potential.
- || Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Review, Journal, Metastases: Resistance to KRAS inhibition in advanced non-small cell lung cancer. (Pubmed Central) - Jun 7, 2024
Currently, there are only two approved targeted therapies (adagrasib and sotorasib) for advanced or metastatic KRAS-mutated NSCLC from the second-line setting onwards. In this narrative review, we will focus on KRAS, its molecular basis, the role of its co-mutations, clinical evidence for its inhibition, putative mutation to resistance, and future strategies to overcome resistance to KRAS inhibition.
- ||| inlexisertib (DCC-3116) / Ono Pharma
Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Monotherapy, Metastases: A Phase 1/2 Study of DCC-3116 in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov) - May 31, 2024
P1/2, N=173, Recruiting, Sponsor: Deciphera Pharmaceuticals LLC
In this narrative review, we will focus on KRAS, its molecular basis, the role of its co-mutations, clinical evidence for its inhibition, putative mutation to resistance, and future strategies to overcome resistance to KRAS inhibition. N=323 --> 173 | Trial completion date: Oct 2024 --> Aug 2028 | Trial primary completion date: Apr 2024 --> Aug 2027
- | Lumakras (sotorasib) / Amgen
Phase classification, Monotherapy: CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - May 28, 2024
P1, N=1200, Recruiting, Sponsor: Amgen
N=323 --> 173 | Trial completion date: Oct 2024 --> Aug 2028 | Trial primary completion date: Apr 2024 --> Aug 2027 Phase classification: P1/2 --> P1
- | Lumakras (sotorasib) / Amgen
Journal, IO biomarker: Molecular basis for antibody recognition of multiple drug-peptide/MHC complexes. (Pubmed Central) - May 23, 2024
Deep mutational scanning validated the structures and revealed distinct levels of mutation tolerance by sotorasib- and HLA-binding residues. Together, our structural information and sequence landscape analysis reveal key features for achieving MHC-restricted recognition of multiple hapten-peptide antigens, which will inform the development of next-generation therapeutic antibodies.
- || Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Review, Journal: Activity and resistance to KRASG12C inhibitors in non-small cell lung cancer and colorectal cancer. (Pubmed Central) - May 21, 2024
In the coming years, there will likely be advancements in the development of more efficacious pharmaceuticals and targeted therapeutic approaches for treating NSCLC and CRC. Consequently, individuals with KRAS-mutant NSCLC may experience a prolonged response duration and improved treatment outcomes.
- | Lumakras (sotorasib) / Amgen
Journal, Real-world evidence, Real-world effectiveness, Real-world: Brief Report: Real-World Efficacy and Safety of (Pubmed Central) - May 15, 2024
Toxicities leading to sotorasib interruption, dose reduction, or discontinuation were common. Sotorasib dose reduction was associated with improved survival, suggesting that sotorasib dose reduction may not compromise efficacy.
- | divarasib (RG6330) / Roche
Journal: Divarasib in the Evolving Landscape of KRAS G12C Inhibitors for NSCLC. (Pubmed Central) - May 13, 2024
Sotorasib dose reduction was associated with improved survival, suggesting that sotorasib dose reduction may not compromise efficacy. Although previously difficult to target, sotorasib and adagrasib are now approved for previously treated NSCLC patients with KRAS G12C mutations...While sotorasib met its primary endpoint
- ||| Lumakras (sotorasib) / Amgen
P4 data, Journal, Adverse events: Post-marketing safety concerns of sotorasib: A disproportionality analysis based on FDA adverse event reporting system. (Pubmed Central) - May 10, 2024
Different SOCs had different types of risk over time. After obtaining marketing authorization, the study identified all potentially relevant adverse event (AE) signals expected to have a reporting frequency higher than anticipated and characterized them during sotorasib treatment.
- | D3S-001 / D3 Bio
Preclinical, Journal: D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities. (Pubmed Central) - May 8, 2024
P1/2
In the presence of growth factors, such as EGF and HGF, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust anti-tumor activity preclinically and translated into promising clinical activity in an ongoing phase 1 trial (NCT05410145).
- Lumakras (sotorasib) / Amgen
Sotorasib-modified KRAS G12C MHC I complex as a target for cancer theranostics (717AB (Convention Center); In-Person) - May 8, 2024 - Abstract #SNMMI2024SNMMI_1990;
In this study, we solved a 3. 1
- ||| Lumakras (sotorasib) / Amgen
Journal, Adverse events: Management of sotorasib-related adverse events and hepatotoxicities following anti-PD-(L)1 therapy: Experience with sotorasib in two French anti-cancer centers and practical guidance proposal. (Pubmed Central) - May 6, 2024
1 The experience with sotorasib might help better prevent, screen and manage sotorasib-related and other KRASG12C inhibitors-related AEs, particularly hepatotoxicity.
- || Krazati (adagrasib) / BMS, MRTX1133 / BMS, Lumakras (sotorasib) / Amgen
Review, Journal: Targeting KRAS in pancreatic cancer. (Pubmed Central) - Apr 30, 2024
The other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor (GEF) Son of Sevenless 1 that drives KRAS. These agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.
- Lumakras (sotorasib) / Amgen
Trial completion, Trial completion date, Trial primary completion date: ROSIE: Rivaroxaban Sotorasib Interaction Study (clinicaltrials.gov) - Apr 30, 2024
P4, N=21, Completed, Sponsor: Radboud University Medical Center
These agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes. Recruiting --> Completed | Trial completion date: Nov 2024 --> Mar 2024 | Trial primary completion date: Nov 2024 --> Mar 2024
- || Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Preclinical, Review, Journal: Emerging Therapies in Kirsten Rat Sarcoma Virus (+) Non-Small-Cell Lung Cancer. (Pubmed Central) - Apr 27, 2024
In this review, we summarize the biology of the KRAS protein and the characteristics of KRAS mutations. We then present current and emerging therapeutic approaches for targeting KRAS mutation subtypes intending to provide individualized treatment for lung cancer harboring this challenging driver mutation.
- ||| AMG 193 / Amgen
Enrollment open: AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (clinicaltrials.gov) - Apr 25, 2024
P1, N=500, Recruiting, Sponsor: Amgen
We then present current and emerging therapeutic approaches for targeting KRAS mutation subtypes intending to provide individualized treatment for lung cancer harboring this challenging driver mutation. Not yet recruiting --> Recruiting
- || Lumakras (sotorasib) / Amgen
Trial primary completion date, Monotherapy: CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - Apr 25, 2024
P1/2, N=1126, Recruiting, Sponsor: Amgen
Not yet recruiting --> Recruiting Trial primary completion date: Sep 2026 --> Dec 2026
- Lumakras (sotorasib) / Amgen
Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRASG12C mutation in China and the US. () - Apr 24, 2024 - Abstract #ASCO2024ASCO_6390;
Sotorasib had cost effect from the perspective of the US. Howere, sotorasib had no cost effect from the perspective of China, and only when the willingness to pay(WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0 to 49%.
- Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Characterization of BTX-10908, a first-in-class, orally bioavailable SOS1 bifunctional degrader for the treatment of KRAS- and RTK-driven cancers. () - Apr 24, 2024 - Abstract #ASCO2024ASCO_4717;
Howere, sotorasib had no cost effect from the perspective of China, and only when the willingness to pay(WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0 to 49%. Our developmental candidate, BTX-10908, displayed robust in vitro and in vivo activity supporting its further development for monotherapy and combination therapies of KRAS and RTK-driven cancers.
- Vectibix (panitumumab) / Amgen, Lumakras (sotorasib) / Amgen
Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator's choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC). (Arie Crown Theater) - Apr 24, 2024 - Abstract #ASCO2024ASCO_2724;
P3
While CodeBreaK 300 was not powered to detect a statistically significant difference in OS, the study showed a trend toward improved OS for patients randomized to soto960+pani. Together with PFS and response rates, these results support the use of soto960+pani as a potential SOC for pts with chemorefractory KRAS G12C-mutated mCRC.
- Therapeutic implications of acquired high tumor mutational burden (TMB-H) after targeted therapy (TT) in metastatic colorectal cancer (mCRC). (Hall A; Poster Bd #: 205) - Apr 24, 2024 - Abstract #ASCO2024ASCO_2611;
In this context, TMB may not be an accurate reflection of tumor immunogenicity as it does not distinguish between clonal and subclonal alterations. Our data suggest that pts w/ acquired TMB-H following TT are unlikely to benefit from ICB.
- Lumakras (sotorasib) / Amgen
Sotorasib plus carboplatin and pemetrexed in KRAS G12C advanced NSCLC: Updated analysis from the international CodeBreaK 101 trial. (Hall B1) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1984;
P1, P3
Our data suggest that pts w/ acquired TMB-H following TT are unlikely to benefit from ICB. Sotorasib plus platinum doublet chemotherapy conferred robust and durable responses with a manageable safety profile in CodeBreaK 101, supporting evaluation of this regimen in the ongoing CodeBreaK 202 phase 3 trial in treatment na
- Keytruda (pembrolizumab) / Merck (MSD), Lumakras (sotorasib) / Amgen
Sotorasib versus pembrolizumab in combination with platinum doublet chemotherapy as first-line treatment for metastatic or locally advanced, PD-L1 negative, KRAS G12C-mutated NSCLC (CodeBreaK 202). (Hall A; Poster Bd #: 514a) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1526;
P3
Approximately 750 patients are planned to be enrolled and recruitment began on November 18, 2023. Contact Amgen Medical Information for more information: .
- HBI-2438 / HUYA Bioscience
Therapeutic activity of a new KRAS G12C inhibitor JMKX001899 in brain metastases: Preclinical models of KRAS G12C -mutant non-small cell lung cancer. (Hall A; Poster Bd #: 494) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1504;
The preclinical models in vivo suggest the new KRAS G12C inhibitor JMKX001899 penetrates the central nervous system and show great inhibition of KRAS G12C -mutant NSCLC with BM, which demonstrates therapeutic activity of JMKX001899 in BM. These data support further development of JMKX001899 in patients with KRAS G12C -mutant NSCLC with BM.
- Lumakras (sotorasib) / Amgen
Final analysis of SCARLET study: A single-arm, phase II study of sotorasib plus carboplatin-pemetrexed in patients with advanced non-squamous, non-small cell lung cancer KRAS G12C mutation. (Hall A; Poster Bd #: 480) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1490;
These data support further development of JMKX001899 in patients with KRAS G12C -mutant NSCLC with BM. Sotorasib in combination with CBDCA/PEM demonstrated favorable ORR with modest PFS and good tolerability in advanced non-Sq, NSCLC patients with KRAS G12C mutation.
- Lumakras (sotorasib) / Amgen
Characteristics and clinical outcomes of US veterans with advanced non (Hall A; Poster Bd #: 445) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1456;
Sotorasib in combination with CBDCA/PEM demonstrated favorable ORR with modest PFS and good tolerability in advanced non-Sq, NSCLC patients with KRAS G12C mutation. In this cohort, KRAS G12C appears to confer a favorable prognosis compared to non-G12C variants, which may be explained in part by the adoption of sotorasib.
- Vectibix (panitumumab) / Amgen, Lumakras (sotorasib) / Amgen
Sotorasib plus panitumumab for pre-treated non-small cell lung cancer with KRAS G12C mutation: A phase 1b study. (Hall A; Poster Bd #: 423) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1435;
P1
This cohort of sotorasib plus panitumumab in pre-treated patients with KRAS G12C advanced NSCLC demonstrated safety consistent with each drug's profile. The ORR appears promising in this pretreated population and may warrant further investigation.
- Krazati (adagrasib) / BMS
Gene expression correlates of adagrasib response in KRAS G12C mutated non-small cell lung cancer (NSCLC). (Hall A; Poster Bd #: 393) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1406;
Expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.
- Tagrisso (osimertinib) / AstraZeneca, Lumakras (sotorasib) / Amgen
Survival and mutational differences based on ESR1 and ESR2 expression in non-small cell lung cancer (NSCLC). (Hall A; Poster Bd #: 390) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1403;
ESR1-H/ESR2-H tumors had the highest MPAS and longest OS and there were SST differences with EGFR and KRAS G12C inhibition. ESR1&2 may play key roles in activating the MAPK pathway and future trials could consider targeted therapy combined with ER inhibition based on ESR1&2 expression.
- Impact of trial eligibility criteria on enrollment to KRAS G12C inhibitor trials in patients with non-small cell lung cancer. (S102) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1122;
EC did not expand after early phase trials demonstrated evidence of safety. These data should guide sponsor and FDA considerations in the development of trial protocols for targeted therapies, as fewer barriers to trial participation would enable trials to be completed more quickly and would improve the generalizability of trial results.
- | Lumakras (sotorasib) / Amgen
Journal: Sotorasib dosing and incremental cost ineffectiveness - implications and lessons for stakeholders. (Pubmed Central) - Apr 24, 2024
These data should guide sponsor and FDA considerations in the development of trial protocols for targeted therapies, as fewer barriers to trial participation would enable trials to be completed more quickly and would improve the generalizability of trial results. No abstract available
- | Lumakras (sotorasib) / Amgen
Journal: ML162 derivatives incorporating a naphthoquinone unit as ferroptosis/apoptosis inducers: Design, synthesis, anti-cancer activity, and drug-resistance reversal evaluation. (Pubmed Central) - Apr 22, 2024
Furthermore, GIC-20 also enhanced the sensitivity of resistant MIA-PaCa-2-AMG510R cells to AMG510, suggesting the great potential of GIC-20 in overcoming the acquired resistance of KRASG12C inhibitors. Overall, GIC-20 represents a novel dual ferroptosis/apoptosis inducer warranting further development for cancer therapeutics and overcoming drug resistance.
- || Review, Journal, PD(L)-1 Biomarker, IO biomarker, Metastases: Targeted therapeutic options in early and metastatic NSCLC-overview. (Pubmed Central) - Apr 16, 2024
Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.
- || Lumakras (sotorasib) / Amgen
PK/PD data, Journal, PD(L)-1 Biomarker, IO biomarker: Hepatotoxicity in patients with non-small cell lung cancer treated with sotorasib after prior immunotherapy: a comprehensive clinical and pharmacokinetic analysis. (Pubmed Central) - Apr 15, 2024
P=N/A
In this preliminary prospective study, sotorasib after PD-(L)1 blockade was associated with severe hepatotoxicity, especially in patients with a short interval between treatments, prior immune-related hepatitis and higher anti-PD-1 plasma concentrations. Our results suggest a minimum interval of 6 weeks between anti-PD-(L)1 and sotorasib to minimize the risk of hepatotoxicity.
- || Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Review, Journal: KRASG12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia. (Pubmed Central) - Apr 13, 2024
Therefore, KRASG12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience.
- | Lumakras (sotorasib) / Amgen
Enrollment change, Trial completion date, Trial initiation date, Trial withdrawal, Trial primary completion date: A Clinical Trial to Evaluate Bioavailability and Effect of Food for Sotorasib in Healthy Participants (clinicaltrials.gov) - Apr 11, 2024
P1, N=0, Withdrawn, Sponsor: Amgen
This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience. N=140 --> 0 | Trial completion date: Jun 2024 --> Sep 2024 | Initiation date: Apr 2024 --> Jul 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Jun 2024 --> Sep 2024
- || Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
Review, Journal: Adagrasib Treatment After Sotorasib-Related Hepatotoxicity in Patients With KRASG12C-Mutated Non-Small Cell Lung Cancer: A Case Series and Literature Review. (Pubmed Central) - Apr 9, 2024
Adagrasib may have a distinct hepatotoxicity profile from sotorasib and is more easily combined with CPIs either sequentially or concurrently. These differences may be used to inform clinical decisions regarding an initial KRASG12C inhibitor for patients who recently discontinued a CPI or experience hepatotoxicity on sotorasib.