Detail

Basic Information Clinical Results Relationship Graph

Gene symbol	CD40LG	Synonyms	CD154, CD40L, HIGM1, IGM, IMD3, T-BAM, TNFSF5, TRAP, gp39, hCD40L	Type of gene	protein-coding
Chromosome	X	Map location	Xq26.3	dbXrefs
Gene perturbation-related omics dataset	PerturbAtlas \| PertOrg
Description	CD40 ligand

Gene symbol	E2F1	Synonyms	E2F-1, RBAP1, RBBP3, RBP3	Type of gene	protein-coding
Chromosome	20	Map location	20q11.22	dbXrefs
Gene perturbation-related omics dataset	PerturbAtlas \| PertOrg
Description	E2F transcription factor 1

GTO ID	GTC3988
Trial ID	NCT03555149
Disease	Colorectal Cancer
Altered gene	E2F1\|CD40LG\|TNFSF9
Therapeutic/Target gene	Therapeutic gene
Therapy	DNA oncolytic virus
Treatment	LOAd703\|delolimogene mupadenorepvec
Co-treatment	Regorafenib
Phase	Phase1\|Phase2
Recruitment status	Terminated
Title	A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Colorectal Cancer (Morpheus-CRC)
Year	2018
Country	United States\|Australia\|France\|Korea, Republic of\|Switzerland
Company sponsor	Hoffmann-La Roche
Other ID(s)	CO39612\|2017-004566-99

Vector information

Vector	adenovirus
Construct	Ad5/35-E2F-delta24
Vector type	novel oncolytic serotype 5/35 adenovirus
Transgene/Inserted gene	CD40L, which includes CD40-mediated tumor cell apoptosis and adaptive immune activation; and 4-1BBL, which enhances immunologic memory and expands natural killer (NK) cells.
Viral genome modification	The gene sequence of trimerized membrane-bound (TMZ)-CD40L, alone or in combination with 4-1BBL (LOAd703), separated by a T2A peptide, was synthesized with a cytomegalovirus (CMV) promoter upstream of the 5′ gene and adenovirus-flanking regions for homologous recombination into adenoviral vectors at both ends.
Vector production method	Viruses were produced by transfection of 293 cells (ATCC), followed by expansion in A549 cells (ATCC). The virus supernatants were purified by CsCl gradient centrifugation and diluted in 20 mmol/L Tris, 25 mmol/L NaCl, and 2.5% glycerol. The viable virus titer was measured using a fluorescence-forming units (ffu) assay. The LOAd(−) is the basic LOAd virus without the CMV transgene cassette.
Additional feature	CD40L\|4-1BBL

Cohort1: Regorafenib

Administration route	intravenous infusion
Pts	24
Age	Adult, Older_Adult
Adverse reactions	18/24(All-cause mortality); 5/19(Blood and lymphatic system disorders; Gastrointestinal disorders; Hepatobiliary disorders; Infections and infestations; Musculoskeletal and connective tissue disorders)
References	PMID: 35856081

Cohort2: Atezolizumab_Imprime PGG_Bevacizumab

Administration route	intravenous infusion
Pts	15
Age	Adult, Older_Adult
Adverse reactions	15/15(All-cause mortality); 1/15(General disorders)
References	PMID: 35856081

Cohort3: Atezolizumab_Isatuximab

Administration route	intravenous infusion
Pts	15
Age	Adult, Older_Adult
Adverse reactions	15/15(All-cause mortality); 5/15(Gastrointestinal disorders; Infections and infestations; Metabolism and nutrition disorders; Respiratory, thoracic and mediastinal disorders)
References	PMID: 35856081

Cohort4: Atezolizumab_Selicrelumab_Bevacizumab

Administration route	intravenous infusion
Pts	6
Age	Adult, Older_Adult
Adverse reactions	4/6(All-cause mortality); 3/6(Cardiac disorders; Gastrointestinal disorders; Nervous system disorders; Respiratory, thoracic and mediastinal disorders; Vascular disorders)
References	PMID: 35856081

Cohort5: Atezolizumab_Idasanutlin

Administration route	intravenous infusion
Pts	4
Age	Adult, Older_Adult
Adverse reactions	4/4(All-cause mortality); 1/4(Blood and lymphatic system disorders)
References	PMID: 35856081

Cohort6: Atezolizumab_Regorafenib

Administration route	intravenous infusion
Pts	15
Age	Adult, Older_Adult
Adverse reactions	11/15(All-cause mortality); 7/15(Blood and lymphatic system disorders; Gastrointestinal disorders; General disorders; Infections and infestations; Neoplasms benign, malignant and unspecified (incl cysts and polyps); Skin and subcutaneous tissue disorders)
References	PMID: 35856081

Cohort7: Atezolizumab_Regorafenib_AB928

Administration route	intravenous infusion
Pts	15
Age	Adult, Older_Adult
Adverse reactions	12/15(All-cause mortality); 7/15(Blood and lymphatic system disorders; General disorders; Immune system disorders; Infections and infestations; Injury, poisoning and procedural complications; Respiratory, thoracic and mediastinal disorders; Skin and subcutaneous tissue disorders)
References	PMID: 35856081

Cohort8: Atezolizumab_LOAd703

Administration route	intravenous infusion
Pts	2
Age	Adult, Older_Adult
Adverse reactions	1/2(All-cause mortality); 1/2(Immune system disorders)
References	PMID: 35856081

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