Suboptimal clinician awareness of appropriate NTRK fusion testing and TRK inhibitor use in solid tumors.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 229-229
Author(s):  
Ryan P. Topping ◽  
Krista Marcello ◽  
Terrence Fagan ◽  
Timothy A. Quill ◽  
Todd Michael Bauer ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Progressive Disease ◽  
Inhibitor Therapy ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Educational Activities ◽  
Time Period ◽  
Trk Inhibitors ◽  
Therapeutic Alternatives ◽  
Selection Of

229 Background: Since late 2018, 2 TRK inhibitors—larotrectinib and entrectinib—have been approved by the EMA and FDA for treating patients with advanced solid tumors harboring an NTRK fusion and progressive disease or no therapeutic alternatives. It is recommended that testing for NTRK fusions occur as early as possible after a diagnosis of advanced disease in patients with solid tumors to inform potential use of TRK inhibitors. Methods: Between April 2018 and April 2021, we conducted multiple live and online educational activities for oncology healthcare professionals (HCPs) on NTRK fusion testing and/or TRK inhibitor treatment for varied solid tumors. Each activity included polling questions designed to assess HCP knowledge and practice patterns. In this analysis, we assessed HCP responses to these questions to evaluate awareness of expert recommendations on NTRK fusion testing and the selection of TRK inhibitor therapy for appropriate patients. Results: In 6 live and online activities with data from April 2018 to April 2021, 29% of HCPs (n = 844) indicated that they ordered molecular profiling to test for NTRK fusions in all solid tumors in their current practice. Of note, low rates of testing were reported in TRK inhibitor/ NTRK testing-focused activities throughout this time period, with no significant increase over time. In assessing different patient cases across 8 activities where experts recommended TRK inhibitor therapy as optimal, many HCPs did not select a TRK inhibitor, with considerable variance by tumor type (Table). *For all cases, experts selected larotrectinib and/or entrectinib as optimal treatment. †HCP respondents. GBM, glioblastoma; GI, gastrointestinal; MSI-H, microsatellite instability-high; PD, progressive disease; PTC, papillary thyroid cancer.Conclusions: The rate of broad testing for NTRK fusions across patients with solid tumors remains low, and many HCPs lack awareness of when to consider a TRK inhibitor. Educational activities designed to address these deficiencies would be of clear benefit to HCPs treating patients with advanced solid tumors. A detailed analysis of HCP trends will be presented.[Table: see text]

Feasibility study of microbial ecosystem therapeutics (MET-4) to evaluate effects of fecal microbiome in patients on immunotherapy (MET4-IO).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2664-TPS2664
Author(s):  
Tira Jing Ying Tan ◽  
Marcus O. Butler ◽  
Aaron Richard Hansen ◽  
David Hogg ◽  
Adrian G. Sacher ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Solid Tumors ◽  
Alpha Diversity ◽  
Nucleic Acid Detection ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Shotgun Metagenomics ◽  
Fecal Microbiome ◽  
Significant Difference ◽  
Group B

TPS2664 Background: Differences in microbiome diversity and composition in immune checkpoint inhibitor (ICI)-responders vs non-responders have been demonstrated. Transplantation of responder feces in mouse models recapitulated the ICI-responsive phenotype. MET-4 is an oral alternative to fecal transplant consisting a well-defined mixture of intestinal bacteria isolated from healthy donor stool sample. We hypothesize that co-administration of MET-4 with ICI is safe and results in alterations of the gut microbiota. Methods: Three cohorts (n = 65) of subjects with any advanced solid tumor type treated with monotherapy anti- PD1/PD-L1 antibody outside of a therapeutic clinical trial will be enrolled. Group A: safety cohort of 5 subjects already on ICI will receive MET-4 in addition to standard of care (SOC) ICI. If < 2 subjects report adverse events of CTCAE grade ≥3 within 4 weeks at least possibly related to MET-4, this dose will be declared safe and groups B/C may start enrolling. Group B (n = 40): subjects with advanced solid tumors starting on ICI, randomized 3:1 to MET-4 plus SOC vs. SOC. Group C (n = 20): subjects with advanced solid tumors already on ICI with first unconfirmed disease progression randomized 1:1 to MET-4 plus ICI continuation vs. continuing ICI. Serial stool samples will be collected for taxonomic composition, diversity, metagenomics content and MET-4 species abundance. We anticipate the following analyses: 16S rRNA sequencing, shotgun metagenomics sequencing, qPCR, Nanostring nucleic acid detection and metabolomics profiling. Serial blood sampling for flow cytometry/CyTOF. Immune microenvironment of tumor specimen will be examined using immunohistochemistry. Other major inclusion criteria: willingness to provide correlative samples, RECIST v1.1 measurable disease and ECOG 0-2. Subjects unable to swallow oral medications are excluded. For the primary objective of cumulative relative abundance and changes of ICI-responsiveness associated species between baseline and day 12 MET-4, assuming a change of 0.5 standard deviation (SD) of microbial alpha diversity, our study will have ≥84% power to identify a significant difference given a significance level at 0.05 in group B. Assuming a change of 0.9 SD of microbial alpha diversity, we will have ≥83% power to identify a significant difference in group C. Response rates and progression free survival will be assessed per RECIST v1.1 and compared with historical data. Clinical trial information: NCT03686202.

Effect of concurrent beta-blocker use in patients receiving immune checkpoint inhibitors for advanced solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15068-e15068
Author(s):  
Vaibhav G. Patel ◽  
Qian Qin ◽  
Bo Wang ◽  
Mahalya Gogerly-Moragoda ◽  
George Mellgard ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Model Systems ◽  
Beta Blockade ◽  
Clinical Activity ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Adrenergic Signaling

e15068 Background: Stress-induced adrenergic signaling suppresses the immune system. In animal model systems, pharmacological beta-blockade stimulated CD8+ T-cell activity, and further, it improved clinical activity of immune checkpoint inhibitors (ICI) in inhibiting tumor growth. Herein, we investigate the effect of beta blockers (BB) on clinical outcomes of patients receiving ICI in advanced solid tumors. Methods: We retrospectively evaluated patients with solid tumors treated with at least 2 doses of ICI at our institution from December 2010 to April 2017. The primary outcome was disease control rate (DCR), as defined by radiographic complete response, partial response, or stable disease, by RECIST 1.1 criteria. The primary predictor was use of BB (β1-selective BB vs. no BB; non-selective BB vs no BB). The primary predictive variable was analyzed using multivariate logistic regression model controlling for several parameters including patient demographics, co-morbidities, ECOG performance status, and tumor type and location of metastases. All tests were two-sided at the significant level of 0.05. Results: We identified 298 evaluable patients with median age of 66.5 (31-95). Of these patients, 200 (67%) did not use BB, 75 (25%) used β1-selective BB, and 23 (8%) used non-selective BB. In multivariate analysis, use of β1-selective BB was significantly associated with improved DCR compared to no BB (ORR 2.43, 95% CI 1.31-4.51, P = 0.005), while use of non-selective BB was not associated with improved DCR (ORR 1.71, 95% CI 0.65-1.47, P = 0.27). Conclusions: The concurrent use of BB may enhance the clinical activity of ICI, particularly β1-selective BB. Our findings warrant further investigation to understand the interaction of β1- and β2-adrenergic signaling and antitumor immune activity, and potentially explore a combination strategy of ICI and BB.

A phase Ia/b study of TIM-3/PD-L1 bispecific antibody in patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2654-TPS2654 ◽  
Author(s):  
Matthew David Hellmann ◽  
Toshio Shimizu ◽  
Toshihiko Doi ◽  
F. Stephen Hodi ◽  
Sylvie Rottey ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Bispecific Antibody ◽  
Checkpoint Inhibitors ◽  
Primary Objective ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Open Label Phase ◽  
Phase 1B

TPS2654 Background: Programmed cell death 1 immune checkpoint inhibitors (anti-PD-1, anti-PD-L1) have demonstrated clinical benefit in a subset of patients with manageable safety across a variety of tumor types. T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) can be co-expressed with PD-1 on exhausted T-cells and may be upregulated in tumors refractory to anti-PD-1 therapy (Koyama et al. 2016). Pre-clinical studies demonstrated that blockade of both PD-1 and TIM-3 improved survival of tumor-bearing mice compared to blocking anti-PD-1 only (Koyama et al. 2016). LY3415244 is a TIM-3/PD-L1 bispecific antibody that has the ability to target and inhibit both TIM-3 and PD-L1 and the potential to overcome primary and acquired anti-PD-(L)1 resistance by a novel mechanism to bridge TIM-3- and PD-L1-expressing cells. Methods: Study JZDA is a multicenter, nonrandomized, open-label, Phase 1a/1b study of LY3415244 in patients with advanced solid tumors. In Phase 1a, subjects with any tumor type who are either PD-(L)1 inhibitor-naïve or exposed are eligible. In Phase 1b, expansion cohorts are planned in subjects with PD-(L)1-experienced NSCLC, urothelial carcinoma, and melanoma. Patients with malignant mesothelioma are not required to have received prior anti-PD-(L)1 therapy. The primary objective is to assess safety and tolerability of LY3415244 and identify the recommended Phase 2 dose (RP2D) in Phase 1a (dose escalation). Safety and tolerability of the RP2D will be assessed in Phase 1b (dose expansion). The secondary objectives are to assess the pharmacokinetics of LY3415244 in Phase 1a/1b and assess early antitumor activity of LY3415244 in Phase 1b cohorts. Pre- and on-treatment biopsies will be obtained to explore potential biomarkers of response. During Phase 1a, dose escalation cohorts will proceed via a modified toxicity probability interval-2 (mTPI-2) design with a 1-cycle (28-day) dose-limiting toxicity (DLT) observation period. LY3415244 will be dosed intravenously every 2 weeks. Data from Phase 1a will determine the RP2D, which will be used for all cohorts in Phase 1b. The study is currently open to enrollment. Clinical trial information: NCT03752177.

BET inhibitor molibresib for the treatment of advanced solid tumors: Final results from an open-label phase I/II study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3618-3618 ◽  
Author(s):  
Sophie Cousin ◽  
Jean-Yves Blay ◽  
Irene Braña Garcia ◽  
Johann S. De Bono ◽  
Christophe Le Tourneau ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Single Agent ◽  
Treatment Discontinuation ◽  
Tolerability Profile ◽  
Repeat Dose ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Total Cohort ◽  
Tumor Types

3618 Background: Molibresib is an orally available, small molecule bromodomain and extra-terminal domain (BET) protein inhibitor under investigation for treatment of advanced solid tumors. Methods: This was an open-label, single- and repeat-dose, 2-part, Phase 1/2 study including patients (aged ≥16 years) with advanced solid tumors. Part 1: patients received different oral doses of molibresib (2–100mg QD; amorphous free-base formulation) to determine recommended Phase 2 dose. Part 2 (expansion cohort): patients with various tumor types received the bioequivalent besylate formulation (75mg) to explore clinical activity at recommended dose. Safety and efficacy (response rate [RR] based on RECIST 1.1 criteria, progression-free survival [PFS], and overall survival [OS]) were evaluated for the total cohort (patients from Part 1 and 2). Safety, pharmacokinetic, pharmacodynamic, and efficacy per tumor type were evaluated in Part 2. Results: Part 1 only data have previously been reported. Overall, 196 patients were included in the total cohort (1 patient in Part 1 was counted twice). In the all treated population, 195 patients (median age 58 years; 46% male) received ≥1 dose of molibresib (Part 1: n = 93; Part 2: n = 102). Adverse events (AEs) were experienced by 193/196 (98%) patients; 180/196 (92%) had a treatment-related AE (TRAE). AEs led to permanent treatment discontinuation in 38/196 (19%) patients. Of different tumor types in Part 2, NUT carcinoma (NC) had the lowest frequency of TRAEs (10/12 [83%]) and AEs leading to permanent treatment discontinuation (1/12 [8%]). In total cohort, 3/31 NC patients and 1/35 with castration-resistant prostate cancer (CRPC) achieved a confirmed partial response. A further 67/196 (34%) achieved stable disease (SD). In Part 2, RR in 12 NC patients was 8% (CI: 0.2–38.5); 50% had SD and median PFS was 4.8 months with median OS of 5.0 months. In CRPC patients, RR was 4% (CI: 0.1–21.9); 22% had SD; median PFS was 8.0 months with median OS of 9.1 months. Plasma concentrations for molibresib and active metabolites were similar between different tumor types. Gene expression analysis from pre- and post-dose biopsy samples collected from 10 mCRPC patients showed transcriptional downregulation of Myc target genes upon treatment with molibresib. Conclusions: Molibresib demonstrated a manageable safety and tolerability profile with single agent activity observed in selected patients with NC and CRPC. Clinical trial information: NCT01587703 .

Trial in progress: A phase 1-2 multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of ABN401 in patients with advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3157-TPS3157
Author(s):  
Dae Ho Lee ◽  
Aflah Roohullah ◽  
Byoung Chul Cho ◽  
Charlotte Rose Lemech ◽  
Paul L. de Souza ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Locally Advanced ◽  
Local Therapy ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Open Label

TPS3157 Background: c-MET (hepatocyte growth factor (HGF) receptor) overexpression, either by gene amplification, or mutation is associated with oncogenic transformation in numerous malignancies including lung, gastric, skin, renal, colorectal, and pancreatic cancers. ABN401 inhibits the activation of c-MET by reversibly interfering with the binding of c-Met tyrosine kinase to adenosine triphosphate (ATP) and blocking the receptor's downstream signaling that has demonstrated efficacy in NSCLC and gastric cancer in mouse xenograft and PDx models. This clinical trial is in progress in patients with advanced cancers. Methods: ABN401 is being evaluated in an open-label, non-randomized, dose-escalation (phase 1) study in patients with advanced solid tumors, and dose-expansion (phase 2) in patients with targeted indications and c-MET biomarker expression (NCT04052971). The phase 1 explores ascending daily doses of oral ABN401 monotherapy in 21-day cycles to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). A preplanned extension (pilot expansion) study has been initiated based on predefined positive efficacy signals at intermediate doses up to 10 NSCLC patients who have c-MET alteration. Once RP2D is determined, the phase 2 expansion of up to 10-29 patients in four specific tumor-type cohorts is planned, utilizing a Simon's optimal two-stage design to evaluate the clinical activity of ABN401. ABN401-001 study began enrolling patients in August 2019 and is ongoing in Korean and Australia. Dose escalation up to cohort 4 has been completed, enrollment to cohort 5 began in November 2020. AEs are assessed according to CTCAE v5. Tumor response is determined according to RECIST 1.1 criteria and safety findings reviewed by the DRC, which will determine the RP2D and MTD. Key Phase 1 eligibility criteria include 1) histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma and 2) refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy. For the extension (pilot expansion) study, patients must have NSCLC with MET exon 14 skipping, MET amplification and/or c-MET overexpression. An exploratory study is being conducted for co-development of a companion diagnostic (CDx) system including a CTC device and ddPCR kit through liquid biopsy. Clinical trial information: NCT04052971.

Preliminary results of molecular screening for FGFR alterations (alts) in the RAGNAR histology-agnostic study with the FGFR-inhibitor (FGFRi) erdafitinib.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4081-4081
Author(s):  
Christophe Massard ◽  
Shubham Pant ◽  
Gopa Iyer ◽  
Martin H. Schuler ◽  
Olaf Witt ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Efficacy And Safety ◽  
Molecular Screening ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Genomic Databases ◽  
Wide Range ◽  
Tumor Types

4081 Background: FGFR alts (mutations and fusions) have been reported in multiple advanced solid tumors at varying frequencies. These alts may function as oncogenic drivers of disease independent of the underlying tumor type. RAGNAR is an ongoing phase 2, histology-agnostic trial investigating the efficacy and safety of erdafitinib, a selective pan-FGFRi, in patients (pts) with advanced solid tumors and FGFR alts. Little is known about the incidence, diversity or predominant FGFR alts across solid tumors in the clinical setting. Here, we provide an update on molecular screening and enrollment in the primary analysis population. Methods: Pts with advanced solid tumors were molecularly screened for eligible FGFR alts via central next generation sequencing (NGS) or review of local NGS reports. Underlying tumor type, FGFR alts, demographics and key disease characteristics were collected at baseline. Results: From Nov 2019 to Jan 2021, 5758 pts were molecularly screened (central or local) in 15 countries. 191 pts (3.3%) fulfilled primary analysis molecular eligibility criteria; 110 pts were enrolled. Among pts enrolled, 14 (12.7%) had central screening and 96 (87.3%) had local NGS reports. Eligible FGFR alts were identified in 19 tumor types, including rare cancers and ones (eg, pancreatic) with a very low prevalence of FGFR alts in genomic databases (Table). Median age was 57 y, and 19 pts (17.3%) were < 40 y. Gender distribution was even. Conclusions: Findings from molecular screening in the RAGNAR study indicate a wide range of FGFR-altered tumor types, including a notable number of cancers where eligible FGFR alts were considered exceedingly rare (eg, pancreatic). These results demonstrate the feasibility of conducting clinical trials on pts with rare genetic alts by adopting a histology-agnostic design and using both central testing and local NGS reports for molecular screening. This approach also helps investigate rare tumors, where histology-specific trials are challenging. Efficacy and safety results from the RAGNAR study will help define the benefit of erdafitinib in FGFR-altered advanced solid tumors. Clinical trial information: NCT04083976. [Table: see text]

Biomarker results supporting selection of RP2D from a phase 1b study of ORIC-101, a glucocorticoid receptor antagonist, in combination with nab-paclitaxel in patients with advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3110-3110
Author(s):  
Anneleen Daemen ◽  
Aleksandr Pankov ◽  
Shravani Barkund ◽  
Haiying Zhou ◽  
Maureen Duff ◽  
...  
Keyword(s):  
Steady State ◽  
Glucocorticoid Receptor ◽  
Solid Tumors ◽  
Preclinical Studies ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Phase 1B ◽  
Cortisol Levels ◽  
Pre Treatment ◽  
Tumor Types

3110 Background: Preclinical studies have shown that activation of the glucocorticoid receptor (GR) leads to resistance to chemotherapeutics (eg taxanes) and antiandrogens across multiple tumor types, while GR inhibition enhances therapeutic efficacy. ORIC-101 is a potent, selective, and orally bioavailable small molecule GR antagonist undergoing clinical development in combination with nab-paclitaxel in patients with advanced solid tumors and in combination with enzalutamide in patients with metastatic prostate cancer. Methods: 21 patients were enrolled in the dose escalation portion of the phase 1b study, which evaluated both intermittent (5 days on, 2 days off for 21 days) and continuous dosing regimens of ORIC-101 across 5 cohorts (NCT03928314). Tumor tissue was obtained pre-treatment for 19 out of 21 patients, and on study or at the end of treatment for 11 patients. GR protein status was retrospectively evaluated using a proprietary IHC assay optimized for staining nuclear GR in the epithelial compartment of major tumor type tissues. Biopsies were also profiled with RNA-seq to evaluate a proprietary GR activation signature as a potentially predictive and pharmacodynamic (PD) biomarker. Blood-derived peripheral blood mononuclear cells (PBMCs) were collected for 20 patients along with the pre-treatment biopsy, in the morning of days 1, 5 and/or 8 of Cycle 1, and 2.5 or 6 hours after ORIC-101 administration. Blood cortisol levels were also simultaneously measured. PD modulation in PBMCs was assessed by RT-qPCR for biomarkers FKBP5, GILZ and PER1, selected for their consistent stimulation by GR and reversal with ORIC-101 in preclinical studies and observed PD modulation in healthy volunteers administered ORIC-101. Results: Nuclear GR protein was detected in most pre-treatment biopsies regardless of tumor type, and on treatment reduction of GR protein was observed across dose levels. At physiological systemic cortisol levels, ORIC-101 demonstrated PD suppression in PBMCs on days 1, 5 and 8 in the majority of patients. Cortisol levels increased post-dose in these patients due to negative feedback between cortisol and GR. Steady-state target engagement was not consistently demonstrated with the intermittent regimen. In healthy volunteer studies of ORIC-101, steady-state target suppression was consistently achieved after 7 consecutive daily doses of 200 or 350 mg of ORIC-101. Thus, continuous ORIC-101 administration was selected as the recommended phase 2 dose (RP2D) regimen, aimed at achieving sustained GR suppression for optimal chemotherapy re-sensitization. Conclusions: Biomarker data from patients enrolled in the phase 1b study provide evidence of on-target tumor cell eradication and PD modulation and support the RP2D and the tumor types selected for the ongoing dose expansion portion of the study. Clinical trial information: NCT03928314.

MyPathway HER2 basket study: Pertuzumab (P) + trastuzumab (H) treatment of a large, tissue-agnostic cohort of patients with HER2-positive advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3004-3004
Author(s):  
Funda Meric-Bernstam ◽  
John Hainsworth ◽  
Ron Bose ◽  
Howard A. Burris III ◽  
Claire Frances Friedman ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Targeted Therapies ◽  
Objective Response ◽  
Tumor Type ◽  
Loading Dose ◽  
Advanced Solid Tumors ◽  
Wild Type ◽  
Her2 Positive ◽  
Molecular Alterations ◽  
Kras Status

3004 Background: HER2 ( ERBB2) amplification and/or overexpression is observed in 2–3% of solid tumors, and is often associated with more aggressive disease. Thus far, HER2-targeted therapies are FDA-approved only for breast, gastric, and gastroesophageal cancers. MyPathway (NCT02091141) is a non-randomized, phase 2a multi-basket study assessing the activity of FDA-approved targeted therapies in non-indicated advanced solid tumors with relevant molecular alterations. We report results from the MyPathway HER2 basket, comprising a large, tissue-agnostic cohort of patients (pts) with HER2-altered tumors treated with P + H. Methods: Pts in this analysis were aged ≥18 years and had HER2-amplified and/or overexpressed tumors. Pts received P (840-mg IV loading dose, then 420-mg every 3 weeks [q3w]) + H (8-mg/kg IV loading dose, then 6-mg/kg q3w). The primary efficacy endpoint was investigator-assessed objective response rate (ORR). Other endpoints included disease control rate (DCR, defined by objective response or stable disease >4 mos) and duration of response (DOR). Subgroup analyses were completed by tumor type and KRAS status. Results: Pts were fully enrolled from April 14, 2014 to June 15, 2020. By January 22, 2021, 260 pts were efficacy-evaluable. Confirmed ORR (cORR) was 23.1% (60/260, including 5 complete responses; 95% confidence interval [CI] 18.1–28.7), DCR was 44.2% (115/260, 95% CI 38.1–50.5), and median DOR was 7.9 mos (95% CI 6.2–9.3). In 199 pts with wild-type KRAS tumors, cORR was 25.6% (51/199, 95% CI 19.7–32.3), DCR was 48.7% (97/199, 95% CI 41.6–55.9), and median DOR was 8.3 mos (95% CI 6.2–10.8). In comparison, in 26 pts with KRAS-mutated tumors, cORR was 3.8% (1/26, responder had colorectal cancer; 95% CI 0.1–19.6), DCR was 3.8% (1/26, 95% CI 0.1–19.6), and DOR was 2.7 mos. KRAS status was unknown in 35/260 pts (cORR 22.9% [8/35, 95% CI 10.4–40.1]; median DOR 6.7 mos [95% CI 2.5–12.7]). Clinical outcomes by tumor type are shown in the Table. Conclusions: P+H was active in a wide variety of KRAS wild-type HER2-amplified/overexpressed tumor types, but had limited activity in KRAS-mutated tumors. Clinical trial information: NCT02091141. [Table: see text]

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