Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors

Abstract Background Monoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion. Envafolimab, a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment, represents a potential advance because it can be conveniently administered subcutaneously. Methods This open-label, single-arm, phase 2 study evaluated the efficacy and safety of envafolimab in patients with previously treated advanced dMMR/MSI-H tumors from 25 clinical sites across China. Adults with histologically confirmed locally advanced or metastatic malignant dMMR/MSI-H solid tumors received weekly 150 mg subcutaneous envafolimab injections in a 28-day treatment cycle. The primary efficacy endpoint was the objective response rate (assessed by a blinded independent review committee). Secondary efficacy outcomes were disease control rate, duration of response, progression-free survival, and overall survival. Results One hundred and three patients (65 with colorectal cancer, 18 with gastric cancer, and 20 with other solid tumors) were enrolled. Median follow-up was 11.5 months. The objective response rate was 42.7% (95% confidence interval [CI] 33.0–52.8), and the disease control rate was 66.0% (95% CI 56.0–75.1). Median duration of response was not reached; the duration of response rate at 12 months was 92.2% (95% CI 77.5–97.4). Median progression-free survival was 11.1 months (95% CI 5.5 to not evaluable). Overall survival at 12 months was 74.6% (95% CI 64.7–82.1). Sixteen patients (16%) had at least one grade 3 or 4 related treatment-emergent adverse event. No grade 5 treatment-emergent adverse events related to envafolimab were reported. Injection site reactions, all grade 1–2, were reported in nine patients (9%), but there were no infusion reactions. Eight patients (8%) had grade 3 or 4 immune-related adverse events. Conclusions This is the first pivotal phase 2 study to examine the efficacy and safety of a single-domain immune checkpoint antibody in the treatment of cancer. Envafolimab was effective and had acceptable safety in the treatment of previously treated advanced dMMR/MSI-H solid tumors. As the first single-domain PD-L1-targeting antibody administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treatment of cancer. Trial registration ClinicalTrials.gov, NCT03667170. Registered 10 September 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03667170.

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Poziotinib in Non–Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial

Journal of Clinical Oncology ◽

10.1200/jco.21.01323 ◽

2021 ◽

Author(s):

Xiuning Le ◽

Robin Cornelissen ◽

Marina Garassino ◽

Jeffrey M. Clarke ◽

Nishan Tchekmedyian ◽

...

Keyword(s):

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Small Cell Lung ◽

Free Survival ◽

Duration Of Response ◽

Previously Treated Patients ◽

Previously Treated ◽

Exon 20 ◽

Insertion Mutations

PURPOSE Insertion mutations in Erb-b2 receptor tyrosine kinase 2 gene ( ERBB2 or HER2) exon 20 occur in 2%-5% of non–small-cell lung cancers (NSCLCs) and function as an oncogenic driver. Poziotinib, a tyrosine kinase inhibitor, was evaluated in previously treated patients with NSCLC with HER2 exon 20 insertions. METHODS ZENITH20, a multicenter, multicohort, open-label phase II study, evaluated poziotinib in patients with advanced or metastatic NSCLC. In cohort 2, patients received poziotinib (16 mg) once daily. The primary end point was objective response rate evaluated by independent review committee (RECIST v1.1); secondary outcome measures were disease control rate, duration of response, progression-free survival, and safety and tolerability. Quality of life was assessed. RESULTS Between October 2017 and March 2021, 90 patients with a median of two prior lines of therapy (range: 1-6) were treated. With a median follow-up of 9.0 months, objective response rate was 27.8% (95% CI, 18.9 to 38.2); 25 of 90 patients achieved a partial response. Disease control rate was 70.0% (95% CI, 59.4 to 79.2). Most patients (74%) had tumor reduction (median reduction 22%). Median progression-free survival was 5.5 months (95% CI, 3.9 to 5.8); median duration of response was 5.1 months (95% CI, 4.2 to 5.5). Clinical benefit was seen regardless of lines and types of prior therapy, presence of central nervous system metastasis, and types of HER2 mutations. Grade 3 or higher treatment-related adverse events included rash (48.9%), diarrhea (25.6%), and stomatitis (24.4%). Most patients had poziotinib dose reductions (76.7%), with median relative dose intensity of 71.5%. Permanent treatment discontinuation because of treatment-related adverse events occurred in 13.3% of patients. CONCLUSION Poziotinib demonstrates antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC.

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Pembrolizumab in Patients With Microsatellite Instability–High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study

Journal of Clinical Oncology ◽

10.1200/jco.21.01874 ◽

2022 ◽

Author(s):

David M. O'Malley ◽

Giovanni Mendonca Bariani ◽

Philippe A. Cassier ◽

Aurelien Marabelle ◽

Aaron R. Hansen ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Antitumor Activity ◽

Objective Response Rate ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Free Survival ◽

Duration Of Response ◽

Previously Treated

PURPOSE Pembrolizumab demonstrated durable antitumor activity in patients with previously treated, advanced microsatellite instability–high or mismatch repair–deficient (MSI-H/dMMR) tumors, including endometrial cancer, in the nonrandomized, open-label, multicohort, phase II KEYNOTE-158 study ( NCT02628067 ). We report efficacy and safety outcomes for patients with MSI-H/dMMR endometrial cancer enrolled in KEYNOTE-158. METHODS Eligible patients from cohorts D (endometrial cancer, regardless of MSI-H/dMMR status) and K (any MSI-H/dMMR solid tumor, except colorectal) with previously treated, advanced MSI-H/dMMR endometrial cancer received pembrolizumab 200 mg once every 3 weeks for 35 cycles. The primary end point was objective response rate per RECIST version 1.1 by independent central radiologic review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. RESULTS As of October 5, 2020, 18 of 90 treated patients (20%) had completed 35 cycles of pembrolizumab and 52 (58%) had discontinued treatment. In the efficacy population (patients who received ≥ 1 dose of pembrolizumab and had ≥ 26 weeks of follow-up; N = 79), the median time from first dose to data cutoff was 42.6 (range, 6.4-56.1) months. The objective response rate was 48% (95% CI, 37 to 60), and median duration of response was not reached (2.9-49.7+ months). Median progression-free survival was 13.1 (95% CI, 4.3 to 34.4) months, and median overall survival was not reached (95% CI, 27.2 months to not reached). Among all treated patients, 76% had ≥ 1 treatment-related adverse event (grades 3-4, 12%). There were no fatal treatment-related events. Immune-mediated adverse events or infusion reactions occurred in 28% of patients (grades 3-4, 7%; no fatal events). CONCLUSION Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in patients with previously treated, advanced MSI-H/dMMR endometrial cancer.

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Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2017.75.4648 ◽

2017 ◽

Vol 35 (35) ◽

pp. 3898-3905 ◽

Cited By ~ 133

Author(s):

Martin Dreyling ◽

Armando Santoro ◽

Luigina Mollica ◽

Sirpa Leppä ◽

George A. Follows ◽

...

Keyword(s):

Overall Survival ◽

Safety Profile ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Indolent Lymphoma ◽

Phosphatidylinositol 3 Kinase ◽

Free Survival ◽

Duration Of Response ◽

Grade 3

Purpose Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-α and -δ isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate; secondary end points included duration of response, progression-free survival, and overall survival. In addition, safety and gene expression were evaluated. Results Median age was 63 years (range, 25 to 82 years), and patients had received a median of three (range, two to nine) prior regimens. The objective response rate was 59% (84 of 142 patients); 12% of patients achieved a complete response. Median time to response was 53 days. Median duration of response was 22.6 months, median progression-free survival was 11.2 months, and median overall survival had not yet been reached. The most frequent treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade 3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade ≥3 events included decreased neutrophil count (24%) and lung infection (15%). High response rates to copanlisib were associated with high expression of PI3K/B-cell receptor signaling pathway genes. Conclusion PI3K-α and -δ inhibition by copanlisib demonstrated significant efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory indolent lymphoma.

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Endometriumkarzinom: Kombination aus Lenvatinib und Pembrolizumab zeigt Wirksamkeit unabhängig vom Mikrosatellitenstatus

Karger Kompass Onkologie ◽

10.1159/000520861 ◽

2021 ◽

pp. 1-2

Author(s):

Sarah Matz

Keyword(s):

Endometrial Carcinoma ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Efficacy Analysis ◽

Duration Of Response ◽

Previously Treated Patients ◽

Previously Treated ◽

Prior Systemic Therapy ◽

Grade 3

Purpose: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. Methods: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST. Results: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients. Conclusion: Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile. Trial registration: ClinicalTrials.gov NCT02501096.

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Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.20.02259 ◽

2020 ◽

pp. JCO.20.02259

Author(s):

Paul G. Richardson ◽

Albert Oriol ◽

Alessandra Larocca ◽

Joan Bladé ◽

Michele Cavo ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Free Survival ◽

Duration Of Response ◽

Heavily Pretreated ◽

Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

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Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.8.2739 ◽

1998 ◽

Vol 16 (8) ◽

pp. 2739-2744 ◽

Cited By ~ 193

Author(s):

Y Bécouarn ◽

M Ychou ◽

M Ducreux ◽

C Borel ◽

F Bertheault-Cvitkovic ◽

...

Keyword(s):

Phase Ii ◽

Response Rate ◽

Phase Ii Trial ◽

Sensory Neuropathy ◽

Progression Free Survival ◽

Free Survival ◽

Duration Of Response ◽

Grade 3 ◽

Colorectal Cancer Patients ◽

Peripheral Sensory

PURPOSE To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

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A phase II study of irinotecan combined with S-1 in patients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000070 ◽

2019 ◽

Vol 29 (3) ◽

pp. 474-479

Author(s):

Seiji Mabuchi ◽

Eriko Yokoi ◽

Kotaro Shimura ◽

Naoko Komura ◽

Yuri Matsumoto ◽

...

Keyword(s):

Cervical Cancer ◽

Phase Ii ◽

Response Rate ◽

Phase Ii Study ◽

Progression Free Survival ◽

Recurrent Cervical Cancer ◽

Free Survival ◽

Platinum Based Chemotherapy ◽

Previously Treated ◽

Grade 3

ObjectivesWe conducted a phase II study to investigate the efficacy and toxicities of irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer.MethodsPatients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy were enrolled. Irinotecan (150 mg/m2) was administered intravenously over the course of 90 min on day 1, and S-1 (80 mg/m2) was given orally in two divided doses from days 1 to 14 of a 21 day cycle. The primary endpoint of this phase II study was response rate. Secondary endpoints included safety, progression free survival, and overall survival.ResultsA total of 19 patients were enrolled and treated. The response rate was 29.4%. Grade 3–4 hematologic toxicities were observed in three patients (15.7%). The only grade 3–4 non-hematologic toxicity observed was grade 3 diarrhea. The median progression free survival and overall survival were 3 months and 9 months, respectively.ConclusionS-1 plus irinotecan in a 3 weekly setting is safe and active in women with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy. Future corroborative clinical studies are warranted.

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Vinorelbine Is an Effective and Safe Drug for AIDS-Related Kaposi’s Sarcoma: Results of a Phase II Study

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.7.1550 ◽

2000 ◽

Vol 18 (7) ◽

pp. 1550-1557 ◽

Cited By ~ 40

Author(s):

Guglielmo Nasti ◽

Domenico Errante ◽

Renato Talamini ◽

Giuliano Rizzardini ◽

Marco Fasan ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Objective Response ◽

Kaposi’S Sarcoma ◽

Progression Free Survival ◽

Complete Response ◽

Free Survival ◽

Duration Of Response ◽

Previously Treated ◽

Chemotherapy Patients ◽

Dose Limiting Toxicity

PURPOSE: To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi’s sarcoma (KS). PATIENTS AND METHODS: From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m2 every 2 weeks by intravenous bolus. RESULTS: Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity. CONCLUSION: Vinorelbine is safe and effective in the treatment of patients with advanced KS who have been previously treated with one or more chemotherapy regimens.

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Efficacy of vemurafenib in patients (pts) with non-small cell lung cancer (NSCLC) with BRAFV600 mutation.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9074 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9074-9074 ◽

Cited By ~ 8

Author(s):

Vivek Subbiah ◽

Radj Gervais ◽

Gregory J. Riely ◽

Antoine Hollebecque ◽

Jean-Yves Blay ◽

...

Keyword(s):

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Braf Mutations ◽

Open Label ◽

Braf Inhibition ◽

Duration Of Response ◽

Secondary Endpoints ◽

Prior Systemic Therapy ◽

Grade 3

9074 Background: BRAFV600 mutations occur in 1–2% of pts with NSCLC. We previously reported the efficacy of vemurafenib, a selective BRAFV600 inhibitor, in BRAF mutation-positive non-melanoma tumors (VE-BASKET study). We now present final data for the expanded NSCLC cohort. Methods: This open-label, histology-independent, phase 2 study included 6 prespecified cohorts (including NSCLC) plus one ‘all-others’ cohort. Pts received vemurafenib (960 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (RECIST v1.1). Secondary endpoints included best overall response rate, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Because the pre-specified clinical benefit endpoint was met in the initial NSCLC cohort, the cohort was expanded. ClinicalTrials.gov identifier NCT01524978. Results: Database lock was 12 Jan 2017. Of 208 pts enrolled at 25 centers worldwide, 62 pts had NSCLC: median age 65 years; 56% male; 13% had no prior systemic therapy; 50% had ≥2 prior therapies. Responses were seen in previously treated and untreated pts (Table). The most common all-grade adverse event (AE) was nausea (40%); grade 3–5 AEs included keratoacanthoma (15%) and squamous cell carcinoma of the skin (15%). Six pts discontinued vemurafenib due to AEs; two had non-treatment-related fatal AEs. Conclusions: Vemurafenib showed evidence of encouraging efficacy in pts with NSCLC with BRAFV600 mutation, with prolonged PFS in previously untreated pts; median OS was not estimable due to ongoing responses. The safety profile of vemurafenib was similar to that seen in melanoma studies. Our results suggest a role for BRAF inhibition in NSCLC with BRAF mutations. Clinical trial information: NCT01524978. [Table: see text]

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Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4040 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4040-4040 ◽

Cited By ~ 5

Author(s):

Heinz-Josef Lenz ◽

Sara Lonardi ◽

Vittorina Zagonel ◽

Eric Van Cutsem ◽

M. Luisa Limon ◽

...

Keyword(s):

Clinical Benefit ◽

Low Dose ◽

Objective Response ◽

Progression Free Survival ◽

Complete Response ◽

Free Survival ◽

Duration Of Response ◽

Therapy Option ◽

Grade 3

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]

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