• Open cohorts: NTRK fusions (all tumor types) and ROS1 fusions (all tumors except NSCLC)
• Entrectinib PO 600 mg daily

• HCC
• HR+ Breast cancer
• Cutaneous squamous cell carcinoma
• Basal cell carcinoma

 TVEC intrahepatic Q3W - Pembrolizumab Q3W IV 

• Accepted mutations:
• EGFR
• HER2 --> Closed
• HER3
• Exclusion: NSCLC with EGFR mutation
• Afatinib 40mg/day with increase to 50 mg.

AMG404: A Phase 1 study with AMG 404 (a PD-1 antibody) in patients with advanced solid tumors

• Melanoma
• SCLC
• NSCLC PD-L1 +
• HNSCC PD-L1 +
• Urothelial PD-L1 +
• Gastric/GEJ adone PD-L1 +
• Esophageal, squamous, PD-L1 +
• Cervical PD-L1 +
• HCC
• Merkel Cell Carcinoma
• SCC of the skin
• RCC, clear cell
• Undifferentiated pleiomorphic/malignant fibrous histiocytoma
• Poorly differentiated and/or dedifferentiated liposarcoma
• Alveolar Soft Tissue Sarcoma
• Angiosarcoma
• Thymic carcinoma
• Nasopharyngeal carcinoma, EBV positive
• Mesothelioma
• MSI-H or MMR-deficient tumors

• AMG 404 IV Q4W

• Archival tissue <1y old or fresh biopsy

CVPM087A2101: Phase Ib study of gevokizumab in combination with standard of care anti-cancer therapies in patients with metastatic colorectal cancer, gastroesophageal cancer and renal cell carcinoma

• Esophageal
• Renal cell
• CRC

• Esophageal: 2L
• Renal cell: 2-3L
• CRC: 1L

• Esophageal: prior fluoropyrimidine and platinum. Study treatment: gevokizumab + paclitaxel + ramucirumab.
• Renal cell: prior anti-angiogenic therapy with radiographic progression during this treatment. Study treatment: gevokizumab + carbozantinib.
• CRC 1L: prior adjuvant is allowed if >= 6 months ago. Study treamtent: gevokizumab + mFOLFOX + bevacizumab. (Open for low CRP <10mg/L)

MiMe-A: Multiorgan Metabolic imaging response assessment of Abemaciclib

• Esophageal squamous cell carcinoma --> 1 slots

AMG510: Phase 1/2 open label study with AMG510 monotherapy in subjects with advanced solid tumors with KRAS p.G12C mutation

• KRAS p.G12C mutation
• CRC: progression after 5-FU, oxaliplatin and irinotecan --> Closed
• NSCLC: progression after anti-PD1/anti-PDL1 AND/OR platinum-based combination therapy AND targeted therapy. Not more than 3 prior lines of therapy. --> Closed
• Solid: progression after 1st line or ineligible for 1st line treatment --> Open

Closed

NCT03600883

RAGNAR: A Phase 2 Study of Erdafitinib in Subjects With Advanced Solid Tumors and Selected FGFR Gene Alterations

• FGFR mutations and FGFR fusions (NO amplifications!)
• Central testing allowed for:
•      Low-grade gliomas
•      SCCHN
•      Endometrial
•      Cervix
•      Ovarian
•      squamous NSCLC
•      Esophageal
•      Gastric
•      Breast: only HR+
•      Pancreatic
•      Colorectal
• Oral medication

NCT04083976

KISIMA-01: Phase Ib Study to evaluate the safety, tolerability and anti-tumor activity of ATP128, with or without BI 754091 in patients with stage IV CRC

• Ongoing PR or SD after completion of 1st line SOC therapy (min. 6 months) 
• 1 liver lesion amenable to repeated biopsy
• ATP128: chimeric recombinant protein vaccine
• BI754091: anti-PD1

NCT04046445

BLU-667: A Phase 1/2 study of the highly-selective RET inhibitor, BLU-667, in patients with thyroid cancer, NSCLC and other advanced solid tumors

• Other solid tumors (except NSCLC): RET fusion

• Other solid tumors (except NSCLC): previously treated with SOC therapy

• Oral medication 

NCT03037385

MCLA-145-CL01: A Phase 1, Open-label, Dose-escalation study of MCLA-145 in participants with advanced or metastatic malignancies 

• Dual CD137 + Anti-PD-L1 antibody 
• Prior anti-PD-1 is allowed (max 1 line)
• Mandatory pre- and on-treatment biopsy
• Specific inclusion criteria for TNBC, melanoma, HNSCC and urothelial carcinoma

NCT03922204

SYD985.004:A Phase 1 study with the antibody-drug conjugate SYD985 in combination with Niraparib in patients with HER2-expressing locally advanced or metastatic solid tumors 

All solid tumors 

• SYD985 IV Q3W + Niraparib oral 
• HER2 tumor status at least 1+ assessed by IHC

NCT04235101

GO40987: A phase I, multicenter, open-label, preoperative, short-term window study of GDC-9545 in postmenopausal women with Stage I-III operable, estrogen receptor-positive breast cancer.

Breast

• ER+/Her2-negative unilateral breast cancer eligible for primary surgery
• Primary tumor >= 1.5 cm
• Postmenopausal women 
• Oral medication QD for 15d prior to surgery 

NCT03916744

INCB86550-102: A Phase 1 study with INCB086550 in patients with advanced solid tumors

• MSI-H/d MMR tumors
• Cutaneaous squamous cell carcinoma
• HCC
• PDL-1 positive esophageal squamous cell carcinoma
• Merkel cell carcinoma
• SCLC
• PDL-1 positive mesothelioma
• Any PDL-1 amplified tumor (9p24.1)
• Nasopharyngeal carcinoma
• Cyclin-dependent kinase 12 mutated tumors (loss of function, not amplification)
• Basal cell carcinoma (unresectable or metastatic)
• RCC with sarcomatoid features
• Clear cell ovarian or endometrial carcinoma
• DNA polymerase epsilon mutated tumors (P286R and V411L)

Other tumor types with approval of Medical Monitor

• Progressed after SOC or intolerant/ineligible for SOC
• No limit to number of prior treatment regims 

• Oral anti-PDL-1
• Mandatory screening + on treatment biopsy 

NCT03762447

eNRGy: Full molecular testing by RNA/DNA next generation sequencing to detect RNA/DNA alterations (including NRG1 fusions) 

• Sponsor: Merus 
• Whole genome sequencing of RNA/DNA (200 genes) 
• ≤ 60 years old at time of diagnosis
• KRAS mutated NOT eligible 
• In case of NRG1 fusion, possibility to enter Early Access Program examining the safety and efficacy of Zenocutuzumab (www.nrg1.com)

BOT112-02: Phase IIa open-label clinical study of intratumoural administration of BO-112 in combination with pembrolizumab in subjects with liver metastasis from colorectal cancer or gastric/gastro-oesophageal junction cancer.

• Arm A: CRC
• Arm B: GC/GEJ

• ARM A: >= 3L
• Arm B: >=2L 

• Pembrolizumab IV Q3W + BO-112 intrahepatic Q3W
• Primarily liver disease
• At least 1 liver m+ of >=20mm suitable for percutaneaous, intra-tumoral injection
• Mandatory on-study biopsy 
• anti-PD(L)-1 naive 

Precision-2 olaparib: Efficacy of Olaparib in advanced cancers occurring in patients with germline mutations or somatic tumor mutations in homologous recombination genes.

• HRD mutated tumor 
• except ovarian and BRCA1/2 mutated breast

• Olaparib 300mg BID
• Accepted mutations:
• BRCA1
• BRCA2
• ATM --> Closed
• BARD1
• BRIP1
• CHEK1/2
• MRE11A
• NBN
• PALB2
• RAD50/51B/51C/51D/54L
• FAM175A
• CDK12
• FANCL
• p53 (germline)
• PPP2R2A

MATTERS: A mono-centric, first in-human (FIH), safety and preliminary efficacy study of (neo)adjuvant, model-based, whole-body hyperthermia (WBHT) treatment in advanced solid cancer patients or stage IV (TxNxM1) metastatic pancreatic adenocarcinoma patients

• Cohort A1: Three patients with advanced solid cancer will be subjected to repetitive hyperthermia starting with 2 hours (day 1), 4 hours (day 8) and 6 hours (day 15)
• Cohort A2: The highest whole-body hyperthermia duration with acceptable side effects from cohort A1 will be applied to three additional patients with advanced solid cancer, once a week and for 15 days in total
• Cohort B1: Three pancreatic cancer patients will be subjected to repetitive hyperthermia starting with 2 hours (day 1), 4 hours (day 8) and 6 hours (day 15) using the device and in combination with the standard of care chemotherapy (FOLFIRINOX, FOLFOX, gemcitabine/nab-paclitaxel or gemcitabine alone).
• Cohort B2: The highest whole-body hyperthermia duration with acceptable side effects from cohort B1 will be applied in combination with chemotherapy (FOLFIRINOX, FOLFOX, gemcitabine/nabpaclitaxel or gemcitabine alone) to three additional pancreatic cancer patients, once a week and for 15 days in total

INCB99280-112: A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Select Advanced Solid Tumors

• MSI-high or MMR-deficient tumors (all types except brain)
• Cutaneaous squamous cell carcinoma
• HCC
• DL-1 positive esophageal squamous cell carcinoma
• Merkel cell carcinoma
• SCLC
• PDL-1 positive mesothelioma
• Any PDL-1 amplified tumor (9p24.1)
• Urothelial carcinoma with CPS >= 10%
• Nasopharyngeal carcinoma
• Cyclin-dependent kinase 12 mutated tumors (loss of function, not amplification)
• Basal cell carcinoma (unresectable or metastatic)
• RCC with sarcomatoid features
• Clear cell ovarian or endometrial carcinoma
• DNA polymerase epsilon mutated tumors (P286R and V411L)
• Other tumor types with approval of Medical Monitor

• Progressed after SOC or intolerant/ineligible for SOC
• No limit to number of prior treatment regimens, but maximum 1 line of immune therapy
• Prior anti-PD-L1 is exclusion

• Oral anti-PD-L1
• Mandatory screening + on treatment biopsy

EZH-1201: A Phase I, Open-label Multi-dose Pharmacokinetic and Safety Study of Oral Tazemetostat in Subjects with Moderate and Severe Hepatic Impairment with Advanced Malignancies.

All tumortypes with:

• Moderate hepatic impairment -> slots
• Severe hepatic impairment -> hold 

• Prior SOC 

• Moderate hepatic impairment: bilirubin from 1.5 to 3 x ULN
• Severe hepatic impairment: bilirubin >= 3 x ULN
• Oral tazemetostat
• Intensive PK sampling

NCT04241835

BP42169: An Open-Label Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7293583, A TYRP1-Targeting CD3 T-Cell Engager, in Participants With Metastatic Melanoma

TYRP-positive melanoma

• Progressed after SOC or intolerant/ineligible for SOC
• No limit to number of prior treatment regimens

• TYRP-prescreening on archival/fresh tissue mandatory
• RO7293583 IV Q3W with hospitalization after 1st administration
• Mandatory screening + on treatment biopsy

NCT04551352

ARRAY 818-103: An Open-label Phase 1 Study to Evaluate Drug-Drug Interactions of Agents Co-Administered With Encorafenib and Binimetinib in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors

BRAF V600E/V600K mutated solid tumors

• Progressed after SOC or intolerant/ineligible for SOC
• No limit to number of prior treatment regimens
• Prior BRAF/MEK inhibitor is permitted, except as last line

• Arm 1: CYP probe cocktail (oral) + encorafenib and binimetinib
• Arm 3: modafinil (oral) + encorafenib and binimetinib
• After drug-drug interaction period (first 28 days), patient proceeds with encorafenib and binimetinib

NCT03864042

TRIDENT-1: A Phase 1/2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

• NSCLC with ROS1 rearrangements
• Solid tumors with NTRK rearrangements

• NSCLC: maximum 2 prior TKI’s, maximum 1 prior line of chemotherapy/immune therapy
• Solid: maximum 2 prior TKI’s, no limit on prior lines of chemotherapy/immune therapy

• Oral repotrectinib = novel TKI
• Different cohorts according to prior TKI and chemo/immune therapy

NCT03093116

JZLA/EMBER: A Phase 1a/1b Study of LY3484356 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With ER+ Locally Advanced or Metastatic Breast Cancer and Other Select Non-Breast Cancers

• Part A: ER+/HER2- mBC
• Part B: ER+/HER2- mBC
• Part C: ER+/HER2+ mBC
• Part D: ER+ endometroid endometrial cancer

• Part A: no prior CDK4/6i, max. 1 prior line for advanced disease
• Part B: prior CDK4/5i, max. 2 prior lines for advanced disease with only 1 prior HT
• Part C: min. 2 prior HER2 directed regimens for advanced disease, prior trastuzumab & pertuzumab & TDM-1, no prior CDK4/6i, no prior fulvestrant
• Part D: progression on platinum-based SOC, no prior AI, no prior fulvestrant

• LY3484356 (oral) monotherapy or in combination with other drugs
• Part A: LY3484356 + abemaciclib +/- AI
• Part B: LY3484356 monotherapy
• Part C: LY3484356 + trastuzumab +/- abemaciclib
• Part D: LY3484356 +/- abemaciclib

NCT04188548

BAYER20810/LOXO-17005: A Phase 1/2 Study of the TRK Inhibitor Selitrectinib in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers

• Solid with NTRK fusion
• At least 1 month of age 

• Prior TRK inhibition for which intolerance, progression or unresponsiveness 
• No limit to number of prior treatment regimens 

• Oral liquid suspension
• Intensive PK sampling 

NCT03215511

FIDES-03: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma

• Gastric adenocarcinoma
• HER2 negative
• FGFR2 fusion/amplification or FGFR1-3 mutation as per central testing (liquid biopsy) 

• No prior treatment with FGFR inhibitors 
• Substudy 1: 2/3L
• Substudy 2: 2L

• Mandatory prescreening on liquid biopsy 
• Substudy 1: derazantinib (oral)
• Substudy 2: derazantinib (oral) + paclitaxel (IV QW) + ramucirumab (IV Q2W) 
• Intensive PK sampling 

NCT04604132

A study to examine the value of broad agnostic NGS panel testing versus reimbursed organ-directed NGS: a Belgian Precision study of the BSMO in collaboration with the Cancer Centre – GeNeo

• All (early lines are preferred)

• Sponsor: BSMO
• Patients with advanced/metastatic solid tumors that are candidates for systemic therapy
• 3 clinical scenarios:

1. Patients eligible for locas NGS (reimbursed or local pracitce)

2. Patients not eligible for reimbursed or local NGS testing

3. Patients with no sufficient archival tissue -> liquid biopsy (limited number) 

• Patients should also enter the Precision1 trial (registration on clinical and NGS data) 

BAYER21136: A Multi-indication, Open-label Phase 2 Study of Regorafenib and Nivolumab in Combination in Patients with Recurrent or Metastatic Solid Tumors

• HNSCC IO treated: 2-4L with 1 prior anti-PD(L)1 for which progression
• ESCC: 2L after platinum and/or fluoropyrimidine, no prior taxane or immune therapy
• PDAC: 2-3L after gemcitabine or fluoropyrimidine, no prior immune therapy --> Closed
• BTC: 2-3L after gemcitabine or fluoropyrimidine or platinum or combination, no prior immune therapy  --> Closed
• GMB grade IV / AA grade II: 1st progression after surgery, RT and temozolomide, no prior immune therapy  --> Closed

• Regorafenib PO + nivolumab IV Q4W 

NCT03406871

TAPISTRY/BO41932: Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study

• Cohort A: prior SOC/none available, prior ROS1 inhibitor is exclusion
• Cohort B: prior SOC/none available, prior NTRK inhibitor is exclusion
• Cohort C: prior SOC/none available, prior ALK inhibitor is exclusion
• Cohort D: prior SOC/none available, prior CF137 agonist or checkpoint inhibitor are exclusions
• Cohort E: prior SOC/none available, prior AKT inhibitor is exclusion
• Cohort F: prior SOC/none available, prior doxorubicin > 500mg/m2 and prior trastuzumab emtansine are exclusions
• Cohort H: prior SOC/none available, prior PIK3 inhibitor is exclusion

• Cohort A: entrectinib oral
• Cohort B: entrectinib oral
• Cohort C: alectinib oral
• Cohort D: atzeolizumab IV
• Cohort E: ipatasertib oral, specific mutations
• Cohort F: kadcyla IV, specific, specific mutations
• Cohort H: inavolisib oral, specific mutations

NCT04589845

HR + and HER2 low or - :

- IHC 2+/ISH-

- IHC 1+/ISH- or untested

- IHC 0/ISH- or untested

• HER2 central confirmation necessary
• progressed on min. 2 prior lines ET for mBC
• no prior chemotherapy for aBC/mBC
• no history of (non-infectious) ILD/pneumonitis

• Molecular study, no study treatment
• Blood samples every 6 months and at progression
• Biopsy after first or second progression and prior to next line of therapy

• AZD9833/Placebo + Placebo/Anastrazole + Palbociclib
• De novo m+ allowed
• If adj. ET treatment: min 24 months AI or Tamoxifen
• If adj. AI +/- CDK4/6 inhibitor: PD after min. 12 months completion of adj. therapy

• Recurrence/PD on or within 12m of end of adjuvant AI or PD while on AI for aBC/mBC.
• max. 2 prior ET for aBC/mBC
• max. 1 prior chemotherapy for aBC/mBC
• No prior Fulvestrant, SERDs, AKT, PI3K, and/or mTOR inhibitors
• prior CDK4/6 inhibitors allowed (max. 50% of target)
• Measurable disease per RECIST 1.1 or lytic bone only disease
• FFPE tumour sample available

• PIK3CA mutant
• PD on or within 12 months of completing adjuvant treatment
• Measurable disease per RECIST 1.1
• GDC-0077/Placebo + Fulvestrant + Palbociclib

• unilateral, (T1cN1; T2N1; T3N0) or locally advanced non inflammatory (T3N1; T4; any T and N2-3) or inflammatory (T4d any N)
• mandatory biopsy before Cycle 2
• baseline LVEF > 55%
• ARM A: neo-adj. chemotherapy + trastuzumab + pertuzumab; adjuvant trastuzumab + pertuzumab
• ARM B: neo-adj. chemotherapy + trastuzumab + pertuzumab + atezolizumab; adjuvant trastuzumab + pertuzumab + atezolizumab

MK-3475-756/KEYNOTE-756: A randomized, double-blind, phase 3 study of Pembrolizumab vs Placebo in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy for the treatment of high-risk early-stage ER+/HER2– breast cancer.

• T1c (>= 2cm) or T2 + cN1-N2, or T3-T4 + cN0-N2
• Centrally confirmed ER+/HER2–, grade 3, ductal histology
• Neoadjuvant: 
• Cycle 1-4: Pembrolizumab/Placebo Q3W + paclitaxel QW; 
• Cycle 5-8: Pembrolizumab/Placebo Q3W + AC Q2W.
• Adjuvant: Pembrolizumab/Placebo Q3W + HT

SGNTUC-016: Randomized, double-blind, phase 3 study of tucatinib/placebo in combination with T-DM1 for subjects with unresectable locally-advanced or metastatic HER2+ breast cancer who were previously treated with a taxane and trastuzumab in any setting, separately or in combination (HER2CLIMB-02).

• Progression after last systemic therapy or be intolerant of last systemic therapy;
• HER2 central confirmation prior to randomization;
• Prior treatment with a taxane and trastuzumab in any setting, separately or in combination. Prior pertuzumab is allowed, but not required;
• Measureable or non-measurable disease per RECIST v1.1;
• Patients with or without brain metastases;
• No prior treatment with T-DM1, tucatinib, neratinib, afatinib, DS-8201a, or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent.

CA209-7FL: A randomized, multicenter, double-blind, placebo-controlled phase 3 study of nivolumab/placebo in combination with neoadjuvant chemotherapy and adjuvant ET in patients with high-risk, ER+, HER2- primary breast cancer (Checkmate-7FL).

• T1c-T2 (≥ 2 cm) and N1-N2; or T3-T4 and N0-N2. Multifocal or inflammatory BC is allowed;
• Centrally assessed: ER+ with or without PR expression;
• Grade 2 with ER expression level 1-10% or Grade 3;
• Neoadjuvant: 
• cycle 1-4: nivolumab 360mg /placebo Q3W + paclitaxel QW
• cycle 5-8: nivolumab 360mg/placebo Q3W + AC Q3W, or nivolumab/placebo 240mg Q2W + AC Q2W.

• Adjuvant: 
• nivolumab/placebo 480mg Q4W + ET.

DESTINY-05: A phase 3, multicenter, randomized, open-label, active-controlled study of trastuzumab deruxtecan (T-DXd) vs T-DM1 in subjects with high-risk HER2-positive primary breast cancer who have residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy.

• HER2+ centrally confirmed prior to randomization.
• Operable at presentation: cT1-3,N0-1,M0, with axillary node positive disease (ypN1-3) following neoadjuvant therapy.
• Inoperable at presentation: cT4,N0-3,M0 or T1-3,N2-3,M0. 
• At least 6 cycles of neoadjuvant chemotherapy (min 16 weeks in total), including min. 9 weeks of trastuzumab + min. 9 weeks of taxane based chemotherapy.
• No prior treatment with T-DXd, T-DM1 or other anti-HER2 antibody-drug conjugate.

FUCHSIA: An open-label, single arm, prospective, multi-center, tandem two stage designed, phase II study to evaluate the efficacy of Fulvestrant in women with recurrent/metastatic estrogen receptor positive gynecological malignancies

• Recurrent or metastatic low grade uterine sarcomas, low grade endometrial carcinomas, sex cord tumors and low grade serous ovarian cancer
• Estrogen-receptor (ER) positive
• Hormonal therapy must have lasted for at least 3 months
• Fulvestrant treatment 

HPV001/APOLLO: A Phase 1b/2, Randomised, Placebo-controlled, Dose-ranging Study to Evaluate Safety, Tolerability and Immunogenicity of a Chimpanzee Adenovirus (ChAdOx1)-vectored Multigenotype High Risk Human Papillomavirus (hrHPV) Vaccine and Modified Vaccinia Ankara (MVA)-vectored Multigenotype hrHPV Vaccine in Women with Low-grade HPV-related Cervical Lesions

• Persistent high-risk HPV infection
• With cevical LSIL: CIN1 or HPV-related change only
• >= 25y and <= 55y old

• Randomized trial: vaccination vs placebo
• injection on D0 and D25 with in-clinic visits in between and afterwards 

MK-3475-A18/ENGOT-cx11: Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer 

• Locally advanced is defined as: FIGO IB2-IIB with positive pelvic or para-aortic lymph nodes or FIGO III-IVa
• 1:1 randomisation: chemoradiation (cisplatin QW) + pembrolizumab Q3W or placebo Q3W
• Carboplatin is not allowed in the study

• Aspirin versus placebo
• Ro resection
• >45year
• stage II-III

SPOTLIGHT: A Double-Blind, Randomized, efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6

• Claudin 18.2-Positive on central lab
• HER2-Negative
• Locally Advanced Unresectable or Metastatic Adenocarcinoma

CAIRO 5: Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases

• Available KRAS/BRAF status mutation prior randomisation
• RAS WT: Folfox/folfiri + beva versus pani 
• RAS MUTANT: Folfox/folfiri versus folfoxiri + beva Liver expert panel will evaluate resectability status --> Closed

DZB-CS-301: A pivotal study of derazantinib in patients with inoperable or advanced intrahepatic cholangiocarcinoma

Intrahepatic CholangioCA

• Pre-screening on FGFR2 gene fusions (closed) or FGFR2 gene mutations or amplifications who received at least one prior regimen of systemic therapy

LEAD-IN FOLICOLOR Trial: Detection of progressive disease in metastatic colorectal cancer patients by NPY methylation in liquid biopsies.

Unresectable metastatic colorectal cancer 

PROMETCO

Metastatic colorectal cancer

CL3-95005-007

• Arm 1: Trifluridine/tipiracil (oral) mono

   

• Arm 2: Trifluridine/tipiracil with bevacizumab
• Randomized (1:1), open-label, phase III study 
• Known RAS status
• Progression or intolerance on maximum 2 prior chemotherapy regimens
• Prior treatment regimens must have included a fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF and/or an anti-EGFR monoclonal antibody for RAS wild-type

MOUNTAINEER

Unresectable or metastatic Colorectal Cancer

• Arm 1: Tucatinib (oral) + Trastuzumab 

• Arm 2: Tucatinib mono 

• Randomized (1:1), open label, phase II study 

• Cross-over is possible 

• Must have progressed on or been intolerant to treatment with 5-FU, oxaliplatin, irinotecan, anti-VEGF. Previously treated with anti-HER2 target is exclusion.

• RAS wild-type, HER 2+ 

• Be able to swallow pills 

YO42137

• Arm A: Tiragolumab + atezolizumab
• Arm B: Tiragolumab + placebo 
• Arm C: placebo + placebo 
• Randomized (1:1:1), double-blind, phase III study 
• Stage II-IVA esophageal squamous cell (8th edition) 
• Received at least 2 cycles platinum-based chemo and radiation consistent with definitive treatment without evidence of disease progression 
• Randomization must occur with 1-63 days after last dose definitive concurrent chemo radiotherapy  

QBGJ398-301/PROOF trial

• Arm 1: Infigratinib (oral) 
• Arm 2: Gemcitabine + Cisplatin 
• Randomized (1:1), open label, phase III study 
• FGFR2 gene fusion/translocation  

MK7339-003

Unresectable or metastatic colorectal cancer without progression on 1ste line FOLFOX

1

• Arm 1: Olaparib (oral) + Bevacizumab
• Arm 2: Olaparib mono 
• Arm 3: 5-FU + bevacizumab 
• Randomized (1:1:1), open-label, phase III study 
• Has not progressed after completing at least 6 prior induction cycles of FOLFOX + bevacizumab and can no longer tolerate oxaliplatin  

FRESCO-2

>3

• Arm 1: Fruquintinib (oral) + BSC 
• Arm 2: placebo + BSC 
• Randomized (2:1), double-blind study, phase III study 
• Must have progressed on or been intolerant to treatment with TAS-102 and / or regorafenib, 5-FU, oxaliplatin, irinotecan, anti-VEGF, if RAS wild-type an anti-EGFR.

D-US-60010-001/NAPOLI-3

• Arm 1: irinotecan liposome injection + oxaliplatin + 5-FU/LV
• Arm 2: nab-paclitaxel + gemcitabine  
• Randomized (1:1), open-label, phase III study 
• Initial diagnosis < 6 weeks prior screening 

MATTERHORN (D910GC00001)

• neo-adjuvant Durvalumab/placebo (D1) + FLOT (D1+D15) Q4W x 2 cycles
• surgery 
• adjuvant Durvalumab/placebo(D1) + FLOT (D1+D15) Q4W x 2 cycles
• Double-blind phase 3 trial
• Stage II or higher (per AJCC 8th edition)
• Tumor tissue < 3 months prior enrollment must be available for central PD-L1 status

MS202202-0002

• Tepotinib + cetuximab 
• Phase 2 trial
• Resistance to anti-EGFR antibody targeting therapy due to MET amplification
• Anti-EGFR as most recent line before study treatment with PR or CR for at least 4 months or SD for at least 6 months prior progression
• Less than 2 months between last administration anti-EGFR and first dose in this study

• Historical or fresh biopsy required 
• ARM A treatment naïve triptorelin + bicalutamide or standar chemotherapy
• ARM B pretreated: triptorelin + bicalutamide
• Cross-over from Arm A SOC to Arm B possible

SCCHN: 

• oral cavity 
• oropharynx
• hypopharynx
• larynx 

• Fresh tumor core biospy, centrally assessed
• Cohort I2: Pretreated with prior PD(L)1
• Cohort B1: p16 negative and EGFR amplification/mutation or PTEN high or HER2 amplification/mutation
• Cohort B2: p16 negative and cetuximab naïve
• Cohort B3: p16 negative and CCND1 amplification
• Cohort B4: p16 negative and ‘platinum-sensitive’
• Cohort B5: p16 positive oropharyngeal cancer
• Cohort I2: monalizumab + durvalumab vs. physician's choice
• Cohort B1 + B2: afatinib vs. physician's choice
• Cohort B3: palbociclib vs. physician's choice
• Cohort B4 + B5: Niraparib

SCCHN Oropharynx HPV16+

• 1st line: tumors express PD-L1
• 2nd line: progression on or after platinum
• fresh biopsy, if possible
• no prior anti-PD(L)1

SCCHN 

• oral cavity
• pharynx
• larynx
• sinonasal
• nasopharyngeal
• unknown primary

HN9: Randomized Phase II study of Cisplatin + Radiotherapy vs Durvalumab + Radiotherapy followed by Adjuvant Durvalumab vs Durvalumab + Radiotherapy followed by Adjuvant Tremelimumab and Durvalumab in Intermediate Risk HPV-Positive Locoregionally Advanced Oropharyngeal Squamous Cell Cancer

SCCHN Oropharynx p16+

• No induction chemotherapy allowed
• Intermediate risk:
• - T1-2 N1 (smoking ≥ 10 pack years) 
• - T3 N0-N1 (smoking ≥ 10 pack years)
• - T1-3 N2 (any smoking hx) 
• - Arm A: Cisplatin + RT
• - Arm B: Durvalumab + RT + adjuvant Durvalumab
• - Arm C: Durvalumab + RT + adjuvant Durvalumab-Tremelimumab --> closed

JZJB/LIBRETTO-531: A Multicenter, Randomized, Open-label, Phase 3 Trial Comparing Selpercatinib to Cabozantinib or Vandetanib in Patients with Progressive, Advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer 

Thyroid

• Crossover possible
• Patients from 12 yo

INTERLINK-1: A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Patients With Recurrent or Metastatic HNSCC Previously Treated With an Immune Checkpoint Inhibitor

SCCHN: 

• oral cavity 
• oropharynx
• hypopharynx
• larynx

• prior PD-(L)1
• prior platinum failed for R/M or locally advanced
• provide recent tumor tissue

• Topotecan and Cyclophosphamide (TC) --> Hold
• Irinotecan and Temozolomide (IT) --> Closed
• Gemcitabine and Docetaxel (GD) --> Closed
• High dose Ifosfamide (IFOS)
• >=4 years and <50 years

• Estimated to start with chemoradiation ≥ 28 days and ≤ 49 days following surgical resection
• No Prior radiation or chemotherapy
• Total or subtotal resection
• No corticosteroid treatment ≤ 1 week before
• WT1 mRNA-loaded DC vaccination + CRT (temozolomide)

• ≥ 2 bone metastases
• Ongoing androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or bilateral orchiectomy
• Prior docetaxel is permitted under the following conditions: started within 2 months of ADT initiation, given for a maximum of 6 cycles and progression after 6 months of the last dose of docetaxel.
• ARM A: Enzalutamide
• ARM B: Ra223 + Enzalutamide

• T2, T3 or T4a, Nx, N0, N1 or N2, M0
• Cisplatin eligible: R1:1 MVAC+Avelumab or Cis-Gem+Avelumab --> Closed
• Cisplatin ineligible: R1:1 Paclitaxel-Gem+Avelumab or Avelumab --> 1 slot

• cT2-T4aN0M0
• cisplatin ineligible
• TURBT within 12 weeks of randomization
• PD-L1 IHC done centrally
• no urothelial carcinoma of upper urinary tracts
• Arm A: Nivo + NTRK214 - RC - Nivo + NTRK214
• Arm B: Nivo - RC - Nivo
• Arm C: RC only

• HR NMIBC: recurrent T1, high-grade Ta and/or CIS
• Persistent: remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction (note: persistent T1 nog eligible)
• Recurrent: reappearance of HR NMIBC after achieving a CR or tumor free state within 6 months after start of BCG induction. The recurrence must be within 24 months of last exposure to BCG (+56 days).
• Prior cystoscopy/TURBT within 12 weeks prior to randomization.
• For recurrent T1: restaging TURBT between 14-56 days prior to randomization.

• Cutaneous melanoma
• Metastases solely confined within the SN
• CLND or serial nodal observation according to patient decision

• Unresectable stage IIIB-D or IV
• No uveal or ocular melanoma 

• Unresectable stage IIIC-D or IV
• No mucosal, acral, uveal or ocular melanoma
• Cross-over possible

• at least 1 parenchymal brain lesion ≥ 0.5 cm and ≤ 4 cm
• brain metastasis must be asymptomatic
• prior local therapy for brain metastases is allowed
• may have received prior immunotherapy
• no uveal or mucosal melanoma

• Resectable stage IIA (≥ 4cm) to IIIB (T3N2)
• Tissue to be submitted before randomization 

• all subtyes. 
• cT1-3 N0-2 M0.
• 1:1 randomisation to P/D followed by adjuvant 3 cycles platinum-pemetrexed versus neoadjuvant 3 cycles platinum-pemetrexed followed by P/D.

• at least one previous line of platinum-based chemotherapy.
• nivolumab + ipilimumab
• re-challenge possible after PD

• EGFR activating mutation

• MET amplification in TBx, (central or local FISH), or in LBx (central)
• Prior objective clinical benefit to previous osimertinib 
• Radiologic disease progression to previous osimertinib
• Tepotinib + osimertinib or Tepotinib monotherapy

• Arm A: Pralsetinib PO

• Arm B: Carboplatin or cisplatin/pemetrexed; Pembrolizumab/carboplatin or cisplatin/pemetrexed; Carboplatin or cisplatin/gemcitabine 

• Tissue to be submitted (archived/fresh)

• Crossover possible after central confirmed PD

• CEACAM5 >=2+ (centrally assessed)
• prior platinum and immune checkpoint inhibitor
• no previous corneal disorder
• contact lenses are not permitted

NSCLC stage III-IV

• BMI < 20
• weight loss of >2% within 6 prior months
• problems with appetite/eating associated with cancer
• no reversible cause of reduced food intake
• on or off anti-cancer treatment

NCT03743064 

NSCLC

• c-Met+ assessed by IHC (central)
• prior chemotherapy and prior immune checkpoint (N/A if mutant) and prior TKI (sequential lines count as 1)
• pre-screening can be done during prior line
• Non-Sq EGFR WT c-MET high Stage 2
• Non-Sq EGFR WT c-MET intermediate Stage 2
• Non-Sq EGFR Mut c-MET high Stage 1 -> Closed 
• Non-Sq EGFR Mut c-MET intermediate Stage 1 -> Closed
• Squamous -> Closed

NCT03539536 

NSCLC

• stage IIIB - IV
• ALK rearrangement, by FISH or IHC
• treated with at least 1 2nd-generation ALK inhibitor
• samples collected for cohort allocation during screening
• prospective sub-study: 3-monthly LBx during the ongoing response to 2nd-generation ALK inhibitor

NCT04127110 

NSCLC

• stage IIIB-IV
• activating mutation in HER2 exon 20
• prior platinum +/- immune checkpoint inhibitors

NCT04447118