A Phase I Study Evaluating the Safety of Cirtuvivint as Monotherapy and in Combination With ASTX727 and ASTX727 + Venetoclax in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

This phase I trial tests the safety, side effects, and best dose of SM08502 (cirtuvivint) alone and in combination with ASTX727, as well as ASTX727 and venetoclax in treating patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Cirtuvivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 is a combination of two drugs, decitabine and cedazuridine. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving cirtuvivint alone or in combination with ASTX727 or ASTX727 and venetoclax may be safe, tolerable, and/or effective in treating patients with AML and MDS.

Start Date06 Dec 2024

Sponsor / Collaborator

National Cancer Institute

NCT05084859 / TerminatedPhase 1

A Phase 1b, Open-Label, Dose-Escalation, Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Orally Administered SM08502 Combined With Hormonal Therapy or Chemotherapy in Subjects With Advanced Solid Tumors

This study is an open-label, multi-center, dose-escalation, dose expansion study in adult subjects with advanced solid tumors. The study will evaluate the safety, tolerability, PK, and preliminary anti-tumor efficacy of SM08502 administered orally (PO), once daily (QD), following a 5 days on 2 days off treatment schedule in combination with chemotherapy or hormonal therapy. Alternative dosing schedules may be explored in Part 1 if necessary. The recommended Part 2 dose and schedule for each combination will then be further evaluated in the Part 2 expansion.
Dosing will occur in 21- or 28-day cycles (depending on the combination partner) and treatment with SM08502 will continue within each subject unless treatment is discontinued due to toxicity, disease progression, initiation of a new anti-neoplastic therapy, withdrawal of consent, the Sponsor terminates the study, or the subject no longer meets retreatment criteria.

Start Date03 Nov 2021

Sponsor / Collaborator

Biosplice Therapeutics, Inc.

NCT03355066 / TerminatedPhase 1

A Phase 1, Open-Label, Dose-Escalation, Dose-Finding Study Evaluating the Safety and Pharmacokinetics of Orally Administered SM08502 in Subjects With Advanced Solid Tumors

This study is an open-label, multi-center, dose-escalation, dose-finding and expansion study in adult subjects with advanced solid tumors for whom no standard therapy is available. The study will evaluate the safety, tolerability, PK, PD, and preliminary anti-tumor efficacy of SM08502 administered orally, once daily, following a 28-day treatment cycle (Part 1A). Alternative dosing schedules will be explored in Part 1B and the recommended Part 2 dose and schedule will be further evaluated in Part 2.
Subjects will participate in a screening period of up to 14 days. Dosing in 28-day cycles will continue within each subject, unless treatment is discontinued due to toxicity, disease progression, initiation of a new anti-neoplastic therapy, withdrawal of consent, the Sponsor terminates the study, or the subject no longer meets retreatment criteria.
Approximately 10 subjects enrolled in Part 2, irrespective of the tumor type, will be included in a food effect substudy to assess the preliminary effect of a high-fat, high-calorie meal on the PK of SM08502. Subjects participating in the food effect substudy will continue on study and complete assessments as per the Part 2 schedule and receive SM08502 at the recommended Part 2 dose (or another previously assessed dose level and schedule).

Start Date06 Nov 2017

Sponsor / Collaborator

Biosplice Therapeutics, Inc.

100 Clinical Results associated with Cirtuvivint

100 Translational Medicine associated with Cirtuvivint

100 Patents (Medical) associated with Cirtuvivint

Literatures (Medical) associated with Cirtuvivint

06 Apr 2023·bioRxiv : the preprint server for biology

Combination CDC-like kinase inhibition (CLK)/Dual-specificity tyrosine-regulated kinase (DYRK) and taxane therapy in CTNNB1-mutated endometrial cancer.

Author: Watson, Zachary L ; Wolsky, Rebecca J ; Bitler, Benjamin G ; Woodruff, Elizabeth ; Bailey, Courtney ; Danhorn, Thomas ; Corr, Bradley R ; Jordan, Kimberly R ; Moroney, Marisa R

SM08502 (cirtuvivint) is a novel pan CDC-like kinase (CLK) and Dual specificity tyrosine kinase (DYRK) inhibitor that targets mRNA splicing and is optimized for Wnt pathway inhibition. Previous evaluation of single agent CLK/DYRK inhibition (SM04690) demonstrated inhibition of tumor progression and β-catenin/TCF transcriptional activity in CTNNB1-mutant endometrial cancer (EC). In-vitro analysis of SM08502 similarly decreases Wnt transcriptional activity and cellular proliferation while increasing cellular apoptosis. SM08502 is an active single-agent therapy with IC50's in the nanomolar range for all EC cell lines evaluated. Combination of SM08502 with paclitaxel has synergistic effect in vitro, as demonstrated by Combination Index <1, and inhibits tumor progression in four endometrial cancer models (HEC265, Ishikawa, Ishikawa-S33Y, and SNGM). In our in vivo mouse models, Ishikawa demonstrated significantly lower tumor volumes of combination vs SM08502 alone (Repeated Measures one-way ANOVA, p = 0.04), but not vs paclitaxel alone. HEC265, SNGM, and Ishikawa-S33Y tumors all had significantly lower tumor volumes with combination SM08502 and paclitaxel compared to single-agent paclitaxel (Repeated Measures one-way ANOVA, p = 0.01, 0.004, and 0.0008, respectively) or single-agent SM08502 (Repeated Measures one-way ANOVA, p = 0.002, 0.005, and 0.01, respectively) alone. Mechanistically, treatment with SM08502 increases alternative splicing (AS) events compared to treatment with paclitaxel. AS regulation is an important post-transcriptional mechanism associated with the oncogenic process in many cancers, including EC. Results from these studies have led to a Phase I evaluation of this combination in recurrent EC.

01 Mar 2020·Cancer LettersQ1 · MEDICINE

The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models

Q1 · MEDICINE

Article

Author: Yazici, Yusuf ; Chung, Heekyung ; Cho, Shawn ; Mak, Chi Ching ; Chiu, Kevin ; Nguyen, John Duc ; Tam, Betty Y ; Deshmukh, Vishal ; Cahiwat, Joseph ; Eastman, Brian W ; Cha, Steven ; Creger, Emily ; Phalen, Timothy J ; Barroga, Charlene ; Do, Long ; Nguyen, Jackie ; Hood, John ; Chen, Chiao-Wen ; Dellamary, Luis ; Kc, Sunil K ; Bossard, Carine ; Stewart, Josh ; Ghias, Abdullah ; Ibanez, Maureen

The Wnt/β-catenin signaling pathway is aberrantly activated in colorectal (CRC) and many other cancers, and novel strategies for effectively targeting it may be needed due to its complexity. In this report, SM08502, a novel small molecule in clinical development for the treatment of solid tumors, was shown to reduce Wnt pathway signaling and gene expression through potent inhibition of CDC-like kinase (CLK) activity. SM08502 inhibited serine and arginine rich splicing factor (SRSF) phosphorylation and disrupted spliceosome activity, which was associated with inhibition of Wnt pathway-related gene and protein expression. Additionally, SM08502 induced the generation of splicing variants of Wnt pathway genes, suggesting that its mechanism for inhibition of gene expression includes effects on alternative splicing. Orally administered SM08502 significantly inhibited growth of gastrointestinal tumors and decreased SRSF phosphorylation and Wnt pathway gene expression in xenograft mouse models. These data implicate CLKs in the regulation of Wnt signaling and represent a novel strategy for inhibiting Wnt pathway gene expression in cancers. SM08502 is a first-in-class CLK inhibitor being investigated in a Phase 1 clinical trial for subjects with advanced solid tumors (NCT03355066).

Signal Transduction and Targeted Therapy

Cdc2-like kinases: structure, biological function and therapeutic targets for diseases

Review

Author: Qu, Yingzi ; Pang, Luping ; Laster, Kyle Vaughn ; Zhang, Mengmeng ; Dong, Zigang ; Song, Mengqiu

AbstractThe CLKs (Cdc2-like kinases) belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins (SRSF1–12), catalyzing spliceosome molecular machinery, and modulating the activities or expression of non-splicing proteins. The dysregulation of these processes is linked with various diseases, including neurodegenerative diseases, Duchenne muscular dystrophy, inflammatory diseases, viral replication, and cancer. Thus, CLKs have been considered as potential therapeutic targets, and significant efforts have been exerted to discover potent CLKs inhibitors. In particular, clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients, and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic usage. In this review, we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in therapeutics. Our discussion highlights the most recent CLKs research, paving the way for the clinical treatment of various human diseases.

News (Medical) associated with Cirtuvivint

12 Sep 2024

·www.globenewswire.com

Biosplice Therapeutics Announces Initiation of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Trial Sponsored by the National Cancer Institute (NCI)

Biosplice expands its clinical candidate, cirtuvivint, as standalone treatment and combination therapy in patients with AML and MDS, representing next step in ongoing collaboration with the NCISAN DIEGO, Sept. 12, 2024 (GLOBE NEWSWIRE) -- Biosplice Therapeutics, Inc. (“Biosplice”), a clinical-stage biotechnology company pioneering advancements in small molecule inhibition of CDC-like kinases (CLK) and Dual-specificity tyrosine phosphorylation-regulated (DYRK) kinases, is pleased to announce that the U.S. Food and Drug Administration (FDA) has cleared the NCI-sponsored Investigational New Drug (IND) application for cirtuvivint. This small molecule inhibitor of CLK and DYRK kinases is in development for the treatment of hematological malignancies and solid tumors. This clearance allows for the initiation of a new clinical trial of cirtuvivint, both as a standalone treatment for patients with relapsed/refractory AML and MDS as well as in combination with ASTX727 for patients with frontline high-risk MDS. The clinical study (NCI protocol 10674, NCT06484062) will be sponsored by the NCI, part of the National Institutes of Health, with Dr. Maximilian Stahl from the Dana-Farber Cancer Institute serving as principal investigator. This trial will be conducted in participating centers of the NCI’s Experimental Therapeutics Clinical Trials Network including Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. The study aims to enroll up to 52 patients and will be conducted under the Cooperative Research and Development Agreement (CRADA) executed between Biosplice and the NCI. “We are thrilled that the NCI has received FDA clearance to launch this groundbreaking new Phase 1 trial of cirtuvivint in liquid tumors, both as monotherapy and in combination with ASTX727,” stated Dr. Yusuf Yazici, Chief Medical Officer of Biosplice. “This milestone is a major step forward in our efforts to advance innovative treatments targeting CLKs and DYRKs. Given that dysregulated alternative splicing is commonly implicated in AML and MDS, cirtuvivint’s ability to regulate alternative splicing via CLK and DYRK inhibition may provide a promising new therapeutic pathway for patients. Based on compelling anti-tumor activity across both solid and liquid tumors in in vitro and in vivo models, as well as data from two prior Phase 1 trials in solid tumors, cirtuvivint promises to greatly improve outcomes for patients in these critical and underserved areas.” This milestone highlights the ongoing collaboration between Biosplice and the NCI’s Cancer Therapy Evaluation Program (CTEP) through the NCI Experimental Therapeutics (NCI-NExT) program. After extensive evaluation, cirtuvivint was chosen for inclusion by NCI in the NExT programs following a competitive review. NCI-NExT partners with external researchers and leading scientific experts to accelerate the development of the most promising and innovative therapies, guiding them from early-stage research through to regulatory approval. About Biosplice:Biosplice stands at the forefront of research concentrating on the study and regulation of Cdc2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These kinases play pivotal roles in cell cycle regulation, splicing, and neurodevelopment, marking them as critical targets for therapeutic intervention in a range of diseases, including osteoarthritis, cancer, neurological disorders, and diabetes. With a robust chemical platform for kinase inhibition and a deep understanding of kinase signaling pathways, Biosplice leverages cutting-edge technologies to discover and develop highly selective kinase inhibitors. Biosplice’s drugs in clinical development include lorecivivint for osteoarthritis (completed Phase 3) and cirtuvivint for numerous cancers, with a broad preclinical pipeline that encompasses Alzheimer’s disease, diabetes and other degenerative conditions. About Cirtuvivint:Cirtuvivint is a small molecule inhibitor of CLK and DYRK kinases, which are increasingly recognized as key drivers of various cancers. By targeting these kinases, cirtuvivint modulates alternative pre-mRNA splicing, which may reduce the expression of genes vital for tumor growth, survival, and drug resistance. The compound has shown broad anti-tumor activity across a range of solid and liquid tumors in extensive preclinical studies. Cirtuvivint has also been investigated for the treatment of advanced solid tumors in two clinical trials. The first, SM08502-ONC-01 (NCT03355066), was a first-in-human dose escalation study designed to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors. The second, SM08502-ONC-03 (NCT05084859), was a Phase 1b trial assessing the efficacy of cirtuvivint in combination with standard treatments for patients with advanced castration-resistant prostate cancer, advanced non-small cell lung cancer, and advanced colorectal cancer. Learn more at https://www.biosplice.com

Phase 1INDPhase 3

13 Jun 2024

·www.biospace.com

Biosplice Announces Collaboration with Novo Nordisk in Diabetes

Biosplice to leverage leading position in small-molecule DYRK inhibition with Novo Nordisk in a pre-clinical collaboration to develop first-in-class therapies for diabetes. SAN DIEGO, June 13, 2024 (GLOBE NEWSWIRE) -- Biosplice Therapeutics, Inc. (“Biosplice”), a clinical-stage biotechnology company pioneering first-in-class therapeutics based on small-molecule inhibition of DYRK/CLK kinases, has entered a collaboration with Novo Nordisk to develop drug candidates for the treatment of diabetes. This agreement builds upon Biosplice’s innovative research, supported by robust external scientific literature, demonstrating the potential of DYRK inhibition to stimulate β-cell proliferation in animal models and human islet cells, thus offering a promising avenue for diabetes treatment. The collaboration combines Novo Nordisk’s expertise in diabetes and Biosplice’s research and development efforts focused on creating selective and potent DYRK inhibitors. Under the terms of the agreement, Novo Nordisk will fund further preclinical development, with an exclusive option to license Biosplice’s relevant intellectual property primarily focused on cardiometabolic disorders. Specific financial terms were not disclosed, but would include upfront and milestone payments plus royalties for the exclusive license. “We are extremely pleased to combine our unique DYRK inhibition expertise with Novo Nordisk’s leadership in diabetes treatments,” commented Erich Horsley, CFO and CBO of Biosplice. “For over a decade, Biosplice has pioneered the therapeutic potential of highly selective, small-molecule inhibition of DYRK and CLK kinases. Representing over 500 million patients worldwide, diabetes sufferers stand to benefit enormously from developing therapies, such as ours, which hold the promise of restoring the health of human β-cells. We eagerly anticipate unlocking the immense possibilities through our collaboration with Novo Nordisk.” Biosplice management believes that its selective DYRK inhibitors, which have shown encouraging results in animal models and human islet cells, promise excellent potency and safety margins to enable a first-in-class therapy for diabetes treatment. Scientific literature suggests that DYRK kinases play a pivotal role in maintaining the proliferative capacity of β-cells, essential pancreatic cells responsible for producing insulin, a critical hormone regulating blood sugar. Diabetes patients grapple with insufficient insulin production due to a deficiency or dysfunction of pancreatic β-cells. This approach could potentially go beyond currently approved therapies to address the underlying cause of the disease. Biosplice will present publicly some of its preclinical findings from in vivo and in vitro models at the upcoming American Diabetes Association’s conference in Orlando, Florida on June 23 at 12:30 pm. The DYRK kinase has also been implicated as a key driver of harmful aggregation of tau protein, a potential driver of serious neurological conditions. Biosplice has recently announced a collaboration with The Roskamp Institute for traumatic brain injury and is developing lead candidates for the treatment of various tauopathies and neuroinflammatory conditions, including Alzheimer’s disease, frontal temporal dementia and multiple sclerosis. About Biosplice’s Diabetes Program: Biosplice pioneers the development of highly selective and potent DYRK inhibitors to stimulate insulin-secreting β-cell proliferation, a crucial advancement in diabetes treatment. Targeting DYRK holds immense potential in enhancing pancreatic islet function and refining glucose regulation, addressing a key shortfall in both type 1 and type 2 diabetes management. Biosplice's compounds have shown promising results in animal models and human islet cells, amplifying β-cell regeneration and offering renewed hope for effective diabetes therapies. About Biosplice Biosplice stands at the forefront of research concentrating on the study and regulation of Cdc2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These kinases play pivotal roles in cell cycle regulation, splicing, and neurodevelopment, marking them as critical targets for therapeutic intervention in a range of diseases, including osteoarthritis, cancer, neurological disorders, and diabetes. With a robust chemical platform for kinase inhibition and a deep understanding of kinase signaling pathways, Biosplice leverages cutting-edge technologies to discover and develop highly selective kinase inhibitors. Biosplice’s drugs in clinical development include lorecivivint for osteoarthritis and cirtuvivint for numerous cancers, with a broad pre-clinical pipeline that encompasses Alzheimer’s disease, diabetes and other degenerative conditions. Learn more at Corporate Contact: Erich Horsley erich.horsley@biosplice.com

License out/in

18 Apr 2024

·www.biospace.com

Biosplice Announces Upcoming Presentation of Successful OA-07 Phase 3 Long-Term Structure and Pain & Function Results for Lorecivivint for Treatment of Knee Osteoarthritis at OARSI Conference, and...

Biosplice Announces Upcoming Presentation of Successful OA-07 Phase 3 Long-Term Structure and Pain & Function Results for Lorecivivint for Treatment of Knee Osteoarthritis at OARSI Conference, and Completion and Preliminary Analysis of OA-21 Trial 12-Week Pain Results Final analysis of OA-07 results demonstrated statistically significant improvement in joint structure, WOMAC Pain and WOMAC Function, highlighting potential of lorecivivint to be first-in-class, structure-modifying drug for treatment of knee osteoarthritis (OA). Preliminary analysis of OA-21 short-term pain results did not achieve statistical significance SAN DIEGO, April 18, 2024 (GLOBE NEWSWIRE) -- Biosplice Therapeutics, Inc. (“Biosplice”), a clinical-stage biotechnology company pioneering first-in-class therapeutics based on small-molecule inhibition of CLK/DYRK kinases, recently completed two Phase 3 trials, OA-07 long-term structure, pain and function study, and OA-21 short-term pain study. Preliminary results of OA-07 study, initially reported in November 2023, had demonstrated statistically significant and clinically meaningful improvement in joint structure demonstrated by X-ray results of medial joint space width (medial JSW). Final analysis of OA-07 results confirmed this structural benefit and further demonstrated that patients also experienced statistically significant reduction in their pain (as measured by WOMAC Pain at Month 6 and Month 12) and significant improvement in function (as measured by WOMAC Function at Month 12). Biosplice will present its OA-07 results at the Osteoarthritis Research Society International (“OARSI”) World Congress, April 18-21, 2024, in Vienna, Austria. “Patients are desperately seeking a new and safe approach for treating knee osteoarthritis that can provide durable pain relief, improved function, and joint structure benefit,” commented Biosplice Chief Medical Officer, Dr. Yusuf Yazici. “We are very encouraged by our unique data from our OA development program, and especially the recent OA-07 trial, and look forward to sharing these results with the medical community in upcoming meetings.” With respect to the shorter-term OA-21 study, preliminary analysis showed that the study did not meet the primary endpoint of pain reduction at Week 12. The Company observed an unusually high placebo response in this trial compared to published intra-articular OA trials and Biosplice’s prior trials. The Company is currently analyzing these preliminary OA-21 results to further discern what may have caused this result in contrast with the successful OA-07 results, as well as the successful short- and long-term pain and function results of the OA-04 Phase 2 study. The primary goal of Biosplice OA program has been to develop a first-in-class drug that could provide the more than 30 million OA patients in the US, and many more worldwide, with an effective treatment option that would go beyond mere short term pain relief. The cumulative data from Biosplice’s OA program to date, especially in light of the final results of the OA-07 Phase 3 X-ray study, provide strong support in service of this goal. OA-07 study results show that lorecivivint (1) provided a structural benefit in a statistically significant and clinically meaningful manner in moderate and advanced OA patients, a first-in-class attribute among OA treatment options, (2) reduced patients’ pain, (3) improved their function with (4) a remarkably clean safety pro date. With the benefit of these clinical results, Biosplice intends to consult with the US Food and Drug Administration (FDA), as well as regulatory agencies in other countries, for further guidance on the path to marketing approval of lorecivivint. About Biosplice Biosplice stands at the forefront of research concentrating on the study and regulation of Cdc2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These kinases play pivotal roles in cell cycle regulation, splicing, and neurodevelopment, marking them as critical targets for therapeutic intervention in a range of diseases, including osteoarthritis, cancer, neurological disorders, and diabetes. With a robust chemical platform for kinase inhibition and a deep understanding of kinase signaling pathways, Biosplice leverages cutting-edge technologies to discover and develop highly selective kinase inhibitors. Biosplice’s drugs in clinical development include lorecivivint for osteoarthritis and cirtuvivint for numerous cancers, with a broad pre-clinical pipeline that encompasses Alzheimer’s disease, diabetes and other degenerative conditions. Learn more at Corporate Contact: Erich Horsley erich.horsley@biosplice.com

Clinical ResultPhase 3Phase 2

100 Deals associated with Cirtuvivint

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Indication	Highest Phase	Country/Location	Organization	Date
Castration-Resistant Prostatic Cancer	Phase 1	US	Biosplice Therapeutics, Inc.	03 Nov 2021
Castration-Resistant Prostatic Cancer	Phase 1	AU	Biosplice Therapeutics, Inc.	03 Nov 2021
Colorectal Cancer	Phase 1	AU	Biosplice Therapeutics, Inc.	03 Nov 2021
Colorectal Cancer	Phase 1	US	Biosplice Therapeutics, Inc.	03 Nov 2021
Non-Small Cell Lung Cancer	Phase 1	US	Biosplice Therapeutics, Inc.	03 Nov 2021
Non-Small Cell Lung Cancer	Phase 1	AU	Biosplice Therapeutics, Inc.	03 Nov 2021
Advanced Malignant Solid Neoplasm	Phase 1	US	Biosplice Therapeutics, Inc.	06 Nov 2017
Acute Myeloid Leukemia	IND Approval	US	Biosplice Therapeutics, Inc.	12 Sep 2024
Myelodysplastic Syndromes	IND Approval	US	Biosplice Therapeutics, Inc.	12 Sep 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2024	Not Applicable	-	-	Cirtuvivint	esiaijveze(pzqajrddns) = qylrfpzlxy cdbqxrgmbt (zfdqeoqwvt )	-	24 May 2024
NCT05084859 \| NCT03355066 (ESMO2022) Manual	Phase 1	HR-positive/HER2-low Solid Tumors ARV7 Positive	65	cirtuvivint+abiraterone acetate+FOLFIRI-panitumumab/docetaxelFOLFIRI-panitumumab/docetaxel	twaehblmsn(amlxpsntfi) = sljcjlcles zhhgetqlmm (htwvyajckc ) View more	Positive	10 Sep 2022
NCT03355066 (ASCO2019)	Phase 1	Colorectal Cancer	82	SM08502	pzbddsexgc(yoyumwgrkq) = uagdmyquqp sjtpbepuib (pabaybycif ) View more	-	26 May 2019

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