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

CRC

• Cohort 2: MSS or MSI
• Cohort 3 and 4: MSS or MMR proficient

• Cohort 2c: 2L, ongoing PR or SD after completion of 1st line SOC therapy (min. 6 months)
• Cohort 2b and 4b: prior neoadjuvant SOC, no PD on prior neoadjuvant SOC, m+ limited to liver, eligible for en block surgery with curative intent
• Cohort 3 and 4a: 2L, PR or SD after completion of 1st line SOC systemic therapy (min. 4 months) 

• 1 liver lesion amenable to repeated biopsy
• ATP128, VSV-GP128: chimeric recombinant protein vaccine
• BI754091: anti-PD1
• Cohort 2a, 2b, 2c: ATP128 + BI 754091 
• Cohort 3, 4: ATP128 + VSV-GP128 + BI 754091

NCT04046445

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

• Preferred: NSCLC, melanoma, H&N, urothelial cancer or MSI-H/dMMR tumors with PD-L1 >1%, that already received previous anti-PD-L1
• MM approval: solid tumors with PD-L1 >1%

• 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

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

• Adenocarcinoma of the pancreas (≤ 60 years old at the time of diagnosis)

• Sponsor: Merus 
• Whole genome sequencing of RNA/DNA (200 genes) 
• Locally advanced/metastatic
• Has been or is currently being treated with SOC
• No known mutations: ALK, BRAF, EGFR, KRAS, MET, NRAS, RET, ROS1 and absence of known mutations on actionable genes 
• PS 0-2
• In case of NRG1 fusion, possibility to enter Early Access Program examining the safety and efficacy of Zenocutuzumab (www.nrg1.com)

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)
• TMB >10
• 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 -> slots 

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

NCT04241835

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
• 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

• Solid tumors with NTRK rearrangements

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

• 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 C: LY3484356 + trastuzumab +/- abemaciclib
• Part D: LY3484356 +/- abemaciclib

NCT04188548

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

• Cohort A: solid tumors with ROS1 fusion, except NSCLC
• Cohort B: solid tumors with NTRK1/2/3 fusion
• Cohort C: solid tumors with ALK fusion, except NSCLC
• Cohort D: solid tumors with TMB >= 16 --> Hold
• Cohort E: solid tumors with AKT1/2/3 point mutation --> Closed
• Cohort F: solid tumors with HER2 point mutation, except primary CNS (Hold)
• Cohort H: solid tumors with >= 2 PIK3CA point mutations
• Cohort I: solid tumors with class II BRAF mutations/fusions
• Cohort J: solid tumors with class III BRAF mutations
• Cohort K: solid tumors with RET fusion, except NSCLC

• 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 --> Hold
• Cohort E: prior SOC/none available, prior AKT inhibitor is exclusion --> Closed
• Cohort F: prior SOC/none available, prior doxorubicin > 500mg/m2 and prior trastuzumab emtansine are exclusions --> Hold
• Cohort H: prior SOC/none available, prior PIK3 inhibitor is exclusion
• Cohort I: prior SOC/none available
• Cohort J: prior SOC/none available
• Cohort K: prior SOC/none available, prior RET inhibitor is exclusion

• Cohort A: entrectinib oral
• Cohort B: entrectinib oral
• Cohort C: alectinib oral
• Cohort D: atzeolizumab IV --> Hold
• Cohort E: ipatasertib oral, specific mutations --> Closed
• Cohort F: kadcyla IV, specific, specific mutations --> Hold
• Cohort H: inavolisib oral, specific mutations
• Cohort I: Belvarafenib oral, specific mutations --> Hold
• Cohort J: Belvarafenib oral, specific mutations --> Hold
• Cohort K: Pralsetinib oral

NCT04589845

BI1472-0001: A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation

• Prior SOC or no SOC available
• Prior RAS, MAPK or SOS1 targeted therapy is not allowed

• Oral study medication
• Intensive PK sampling with overnight hospital stays

NCT04973163

MCLA-129: Phase 1/2 dose escalation and expansion study evaluating MCLA-129, a human anti-EGFR and anti-c-MET bispecific antibody, in patients with advanced NSCLC and other solid tumors

• Cohort B: NSCLC cMet exon 14 skipping mutation
• Cohort C: HNSCC eligible regardless of mutation, the following tumor types with EGFR or cMet mutation (only with medical monitor approval!): GC, GEJ, pancreas, ESCC, GBM and PRCC, NSCLC with rare EGFR mutation
• Cohort D: NSCLC 1L harboring EGFR sensitizing mutations (i.e. Del19, L858R)
• Cohort E: NSCLC >=2L osimertinib resistant + chemo naive 

• Cohort B: ≥ 2L, capmatinib and tepotinib resistant 
• Cohort C: prior SOC or intolerance
• Cohort D: 1L
• Cohort E: >=2L

• MCLA-129 IV Q2W: biospecific monovalent EGFR x cMET antibody
• Mandatory on-treatment biopsy
• Intensive PK sampling with overnight hospital stay
• Cohort B, C: MCLA-129 monotherapy
• Cohort D, E: MCLA-129 + osimertinib

NCT04868877

OPTIMIZE-1: A phase 1b/2 study assessing the safety and efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma

• Mitazalimab (CD40 agonist) IV Q2W + mFOLFIRINOX Q2W
• Mandatory pre- and on- study biopsies

NCT04888312

GO42144: A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation

• CRC
• NSCLC
• All other 

• Oral study medication
• Intensive PK sampling 

NCT04449874

BALLETT: A study to examine the clinical value of comprehensive genomic profiling performed by Belgian NGS laboratories: a Belgian Precision study of the BSMO in collaboration with the Cancer Centre

• Sponsor: BSMO
• Patients with advanced/metastatic solid tumors that are candidates for systemic therapy
• Life expectancy < 12 weeks
• ECOG ≤ 2
• Tumor tissue < 2 years old
• Patients should also enter the Precision-1 trial (Health Data database - Sciensano)
• National ‘Molecular Tumor Board’ provides therapy recommendation based on CGP results

NCT05058937

SGNTUC-019: Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations

• Her2 overexpression/amplification: cervical, uterine and urothelial cancer

• Specific Her2 mutation: breast cancer

• At least 1 prior SOC
• For HR+ Her2-mutated breast: prior CDK4/6 inhibitor in metastatic setting 

• Tucatinib PO BID + Trastuzumab IV Q3W
• Fulvestrant addition for HR+ Her2 mutated breastcarcinoma

NCT04579380

INCB 99318-122: A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Select Advanced Solid Tumors

• MSI-high or MMR-deficient tumors (all types except brain)
• TMB >10
• 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 regimens, but maximum 1 line of immune therapy
• Prior anti-PD-L1 is exclusion

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

NCT04272034

BT5528-100: A Phase I/II study of BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression

• Urothelial cancer
• Ovarian cancer
• NSCLC
• H&N
• TNBC
• Gastric/upper GI

• Prior SOC 
• No limit to number of prior treatment regimens

• No prescreening anymore for EphA2 expression
• BT5528 IV QW or Q2W
• Intensive PK sampling during first cycle

NCT04180371

20210102 (AMG552): A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Bemarituzumab Monotherapy and Combination with Docetaxel in Subjects with Squamous-Cell Non-Small-Cell Lung Cancer (FORTITUDE-201)

• Squamous cell lung carcinoma
• Centrally confirmed FGFR2b overexpression

• Part 1 and 2: at least 1 prior regimen
• Part 3: at least 2 prior regimens
• Part 4: no prior therapy in metastatic setting
• Prior treatment must include platinum chemotherapy and checkpoint inhibition, and targeted therapy (if applicable)

• Prescreening for FGFR2b overexpression determination
• Part I and 2: bemarituzumab IV Q3W + docetaxel IV Q3W
• Part 3: bemarituzumab IV monotherapy Q2W
• Part 4: bemarituzumab IV Q3W + pembro IV Q3W + (nab)-paclitaxel/carboplatin IV Q3W

AMG 20190135: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation

• Subprotocol F, all cohorts: NSCLC
• Subprotocol H: 
• Cohort C: NSCLC
• Cohort D, F, G: CRC

• Subprotocol F: 
• Cohort B: prior platinum and/or anti-PD(L)-1 and targeted therapy (if applicable)
• Cohort A1: 1st line (no prior platinum, no prior anti-PD(L)-1)
• Cohort A2: prior anti-PD(L)-1 mono or prior platinum-based combination

• Subprotocol F:
• Cohort B: sotorasib + doxetaxel
• Cohort A1 and A2: sotorasib + carboplatinum + pemetrexed

CL1-95012-001: A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors

• Prior SOC, no restriction on number
• Prior anti-PD(L)-1 is allowed

• PRS-344/S095012 IV Q2W
• Intensive PK sampling during cycle 1 and 2

20210023 (AMG193): AMG 193, Methylthioadenosine (MTA) Cooperative Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, Alone and in Combination With Docetaxel in Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (MTAP) 

• Solid tumors
• MTAP-null and/or CDKN2A-null, or lost MTAP expression (local testing)

• Prior SOC or ineligible

• AMG193 oral

XL092-001: A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL092 as Single-Agent and Combination Therapy in Subjects with Inoperable Locally Advanced or Metastatic Soli

• Cohort A (ccRcc)
• Cohort B (nccRCC)
• Cohort E (nccRCC)
• Cohort F (HR+BC)
• Cohort G (mCRPC)
• Cohort H (CRC): KRAS/NRAS wild type

• Cohort A, B, E, F: 1-3 prior lines
• Cohort G: 1-4 prior lines
• Cohort H: prior SOC 

• XL092: a small molecule inhibitor of RTKs, primarily targeting MET and VEGFR2 
• Cohort A, B: XL092 
• Cohort E, F, G: XL092 + atezolizumab 

20210104 (AMG 552): A Phase 1b/2, Multicenter, Open-label Basket Study Evaluating the Safety and Efficacy of Bemarituzumab Monotherapy in Solid Tumors with FGFR2b Overexpression (FORTITUDE-301) 

• Head and Neck Squamous Cell
• Squamous esophageal
• Triple-negative breast
• Pancreatic ductal adenocarcinoma
• Intrahepatic cholangiocarcinoma
• Colorectal 
• Platinum-resistant Ovarian epithelial
• Endometrial
• Cervical
• Other FGFR2b+ solid tumors, except for primary CNS tumors, squamous NSCLC, gastric and GEJ adenocarcinoma 

• TNBC, CRC: at least 2 lines
• All other tumor types: at least 1 line

• Bemarituzumab (AMG 552): a monoclonal antibody against FGFR2b, IV Q2W
• Pre-screening for central IHC FGFR2b overexpression (tissue <10y)

WP43295: A phase 1a/b open-label study to evaluate safety, pharmacokinetics, and preliminary clinical activity of RO7276389 alone and in combination with cobimetinib in participants with BRAF-V600 mutation-positive advanced solid tumor or BRAF-V600 mutation-positive melanoma with central nervous system metastases

• Part 1: Metastatic or locally advanced solid tumors with BRAF-V600 mutation
• Part 2: Cutaneous melanoma with asymptomatic brain metastases 

• RO7276389: a potent RAF inhibitor targeting mutant BRAF V600E/K protein
• Part 1a, part 2 cohorts 1 & 2: monotherapy RO7276389
• Part 1b, part 2 cohorts 3 & 4: combination RO7276389 with cobimetinib

61186372GIC2002 (ORIGAMI-1): A Phase 1b/2, Open-Label Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants with Advanced or Metastatic Colorectal Cancer

• Cohort A, B, C: 3-4 L
• Cohort D, E: 2L

• Amivantamab: an antibody directed against EGF and MET receptors
• Cohort A, B, C: amivantamab monotherapy
• Cohort D: amivantamab + mFOLFOX6
• Cohort E: amivantamab + FOLFIRI

TES16382: Open-label study evaluating the effect of tusamitamab ravtansine on the QTc interval in participants with metastatic solid tumors

• Pre-screening for CEACAM5 expression, required for NSCLC and GC/GEJ
• No pre-screening required for CRC 
• Tusamitamab ravtansine (90 min IV, Q2W)

20200469: A Phase 1b Study Evaluating the Safety and Efficacy of First-Line Tarlatamab in Combination With Carboplatin, Etoposide, and PD-L1 Inhibitor in Subjects with Extensive Stage Small Cell Lung Cancer

• Part 1, 2, 3: AMG757 (tarlatamab) + carboplatin/etoposide + atezolizumab
• Part 5: AMG757 (tarlatamab) + atezolizumab 

MK6482-016: An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Multiple Solid Tumors

• Cohort A: HCC
• Cohort B: CRC
• Cohort C: pancreas
• Cohort D: biliary tract
• Cohort E: endometrium
• Cohort F, G: ESCC

• Cohort A: 1L
• Cohort B: 3L
• Cohort C: 2L
• Cohort D: 2L
• Cohort E: 1L, non-MSI-H
• Cohort F: 2L, IO naïve
• Cohort G: 2L, IO refractory

• Pembrolizumab Q6W + lenvatinib + belzutifan
• Belzutifan: inhibitor of HIF-2α
• Lenvatinib: inhibitor of VEGFR1-3

KBA1412-101: A Phase I, first-in-human, multicenter, open-label, dose escalation followed by an expansion phase clinical study of KBA1412 given as monotherapy or in combination with pembrolizumab in adults with advanced solid malignant tumors 

• Part A: all solid tumors
• Part B, C: melanoma, ovarian cancer, gastric cancer, CRC

• Part A: All
• Part B, C: Prior PD(-L)1 therapy, if this is SOC

• Part A, B: KBA1412 monotherapy
• Part C: KBA1412 + pembrolizumab
• KBA1412 = anti-CD9 human monoclonal antibody, IV

DAY101-102: A Phase 1b/2, Open Label Study of DAY101 Monotherapy or Combination with Other Therapies for Patients with Recurrent, Progressive, or Refractory Solid Tumors Harboring MAPK Pathway Aberrations

• DAY101 monotherapy
• DAY101: oral type II pan-RAF kinase inhibitor
• Archival tissue <1y old

DO2.22.01: A Phase 1 Study to Determine the Safety, and Pharmacokinetics of the Selective MET kinase Inhibitor, DO-2 in Patients With Advanced or Refractory Solid Tumours

• Treatment naive with no current options
• Prior SOC (prior MET inhibitor without PD is allowed)
• Intolerance

• DO-2: Oral MET kinase inhibitor

INCA0186-101: A Phase 1, Open-Label, Multicenter Study of INCA00186 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors

• Cohort A: INCA00186 monotherapy
• Cohort C: INCA00186 + INCB105385 + Retifanlimab 
• INCA00186: mAb that binds CD73, IV Q2W
• INCB105385: oral antagonist of A2A and A2B receptors, QD
• Retifanlimab: anti-PD-1, IV Q4W
• Mandatory pre-screening biopsy for presence of CD8+ T cells (if negative, patient can participate to backfill cohort)

1403-0011 (Brightline-2): A Phase IIa/IIb, open-label, single-arm, multi-centre trial of BI 907828 for treatment of patients with locally advanced/metastatic, MDM2 amplified, TP53 wild-type biliary tract adenocarcinoma, pancreatic ductal adenocarcinoma, or other selected solid tumours

• BI 907828 monotherapy
• BI 907828: oral MDM2-p53 antagonist, Q3W, 45 mg 
• MDM2 amplification and TP53 wild type on local testing

1412-0003: A phase Ia/Ib, open label, multicentre, dose escalation study of BI 905711 in combination with chemotherapy followed by expansion cohorts in patients with advanced gastrointestinal cancers

• Cohort 1 (CRC): Folfiri + bevacizumab +- BI 905711 (randomisatie 2:1)
• Cohort 2 (PDAC): BI 905711 + Folfiri (of liposomal irinotecan + 5FU/leucovorin)
• BI 905711: Bispecific antibody targeting TRAILR2 and CDH17
• Fresh biopsy or archival tissue <6m old

NCT05087992

• 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 --> on HOLD
• 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

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

• HER2+ must be centrally confirmed
• No prior therapy in m+ setting
• 3 study arms (1:1:1)
• ARM 1: T-DXd + Pertuzumab
• ARM 2: T-DXd + Placebo
• ARM 3 : Taxane (paclitaxel QW or docetaxel Q3W) + Trastuzumab + Pertuzumab

Module 1: 0-2L --> on Hold

Module 2: 1L

Module 3: 0-2L

• Participation in Part 2 TNBC modules:
• Module 1: T-DXd + capecitabine
• Module 2: T-DXd + durvalumab + paclitaxel
• Module 3: T-DXd + capivasertib

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.

lidERA: a phase III, randomized, open-label, multicenter study evaluating the efficacy and safety of adjuvant giredestrant compared with physician's choice of adjuvant endocrine monotherapy in patients with estrogen receptor positive, her2-negative early breast cancer

• Medium and high risk stage I-III 
• Arm A: giredestrant QD
• Arm B: ET per SOC 

AL-2001 (Allarity): Phase II, open label, single arm study to investigate anti-tumor effect of ixabepilone in patients with locally recurrent or metastatic breast cancer (mBC)

• Ixabepilone
• DRP score centrally confirmed.
• Patient must have received a taxane and an anthracycline, unless not indicated
• Number of ET does not matter

R4018-ONC-1721: Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer 

• At least 1 prior platinum line for which progression

• REGN4018 IV QW as monotherapy OR REGN4018 IV QW + cemiplimab IV Q3W
• Mandatory screening biopsy
• Very intensive study with mandatory hospitalization after the first 3-6 REGN4018 administrations (depending on cohort)
• Very intensive PK sampling

FLORA-5: Oregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery

• Ovarian: stage III or IV
• BRCA1/2 negative

• New diagnosis
• After (interval) debulking surgery (with R0 or R1 resection)

• Oregovomab = anti-CA-125 antibody
• Primary debulking: 6 cycles of carbo/paclitaxel + 4 administrations of oregovomab/placebo IV
• Interval debulking: 3 additional cycles of carbo/paclitaxel + 4 administrations of oregovomab/placebo IV

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

A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy 

YO42137 - SKYSCRAPER-07

• 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  

Neoadjuvant Regorafenib in Combination With Nivolumab and Short-course Radiotherapy in Intermediate-risk, Stage II-III Rectal Cancer 

REGINA

• Regorafenib + nivolumab + short-course radiotherapy
• Intermediate-risk stage II-III 

NCT04503694

A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer

AT148006

ASPEN-06

• phase 2: ALX 148 + Trastuzumab + Ramicirumab+ Paclitaxel vs Trastuzumab  +Ramicirumab + Paclitaxel 
• phase 3:  ALX 148 + Trastuzumab + Ramicirumab+ Paclitaxel vs Ramicirumab + Paclitaxel
• HER2 positive tumor
• Progression on or after prior HER2 directed agent + 5FU or platinum containing regimen

NCT05002127

Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression 

AMGEN 20210096 FORTITUDE-101

• Bemarituzumab versus placebo +chemotherapy  (folfox 6)
• FGRF2b central testing by IHC
• HER2 positive tumor is exclusion if known

NCT05052801

Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen 

DS8201-A-U306

DESTINY-gastric-04

• Trastuzumab Deruxtecan versus Ramicirumab+Paclitaxel
• Centrally confirmed HER2- positive tumor (IHC3+ or IHC 2+)
• Progression on or after first line Trastuzumab-containing regimen

NCT04704934

A Trial to Assess Efficacy and Safety of Octreotide (CAM2029) Subcutaneous Depot in Patients With GEP-NET 

HS-19-657

• CAM2029 versus octreotide LAR or lanreotide ATG
• Well-differentiated NET of GEP
• Progression during treatment (including SSAs)

NCT05050942

Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation 

MRTX849 

KRYSTAL-10

• MRTX 849 + cetuximab versus chemotherapy
• KRAS G12C mutation
• Disease progression on 1st line

NCT04793958

Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer

AMGEN 20210098 - FORTITUDE-102

• Bemarituzumab + mFOLOFOX6 + Nivolumab Versus Placebo + mFOLFOX6 + Nivolumab
• No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of mFOLFOX6 with or without nivolumab. 
• FGFR2b overexpression positive as determined by centrally performed immunohistochemistry (IHC) testing
• Prior treatment with (FGF—FGFR pathway is exclusion

NCT05111626

FOLICOLOR Trial: Following therapy response through Liquid Biopsy in metastatic colorectal cancer patients

• Randomized trial: Therapy response CT-scan VS. Liquid Biopsy
• Starting FOLFOX/FOLFIRI + Panitumumab
• No history of anti- EGFR
• RAS/BRAF (V600E) WT
• ECOG 0-2
• > 18 years

NALPAC:

A non-comparative randomized phase 2 study, evaluating the efficacy of 5-FU + Naliri and 5-FU + Nalirinox for metastatic pandreatic ductal adenocarcinoma

• Randomized trial 1:1: 
• Arm A (standard of care arm): nal-IRI + 5-FU/LV (NALIRI)
• Arm B (experimental arm): nal-IRI + 5-FU/LV + OxaliplatinECOG 0-2
• Progression After 1L gemcitabine mono OR gemcitabine/abraxane

COLIPAN: 

Collection of Liquid Biopsies in Pancancer patients

• Liquid Biopsy collection new diagnoses 
• No NET-tumours

SCCHN: 

• oral cavity 
• oropharynx
• hypopharynx
• larynx 

• Fresh tumor core biospy, centrally assessed
• Cohort I2: Pretreated with prior PD(L)1 --> Closed
• Cohort I3: Last treatment line was PD(L)1
• Cohort B1: p16 negative and EGFR amplification/mutation or PTEN high or HER2 amplification/mutation --> closed
• 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 --> closed
• Cohort I2: monalizumab + durvalumab vs. physician's choice
• Cohort I3: INCAGN01876
• Cohort B1 + B2: afatinib vs. physician's choice
• Cohort B3: palbociclib vs. physician's choice
• Cohort B4 + B5: Niraparib

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

TACTI-003 (Two ACTive Immunotherapeutics): A multicenter, open label, randomized, Phase II trial to investigate a soluble LAG-3 fusion protein, eftilagimod alpha (efti; IMP321) in combination with pembrolizumab (PD-1 antagonist) for first line treatment of subjects with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) 

Recurrent or metastatic squamous cell carcinoma of the H&N 

• CPS >= 1 : Efti + pembrolizumab vs pembrolizumab mono
• CPS < 1 : Efti + Pembrolizumab
• Disease progression on 1st line

ProcemISA: A Phase II Study of cemiplimab, an anti-PD-1 monoclonal antibody, and ISA101b vaccine in patients with recurrent/metastatic HPV16- positive Oropharyngeal Cancer who have experienced disease progression with prior anti-PD-1 therapy

SCCHN Oropharynx HPV16+

• Recurrent/ metastatic
• Local HPV16 PCR or ISH
• Must have previously received at minimum 600 mg pembrolizumab or 960 mg nivolumab for 1L or 2L
• Last dose IO not more than 6 months prior to first dose in trial and should be last regimen
• PD on or after IO
• 4 x ISA101b vaccin + Cemiplimab q3w

ELEVATE: A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma

SCCHN:

• oropharynx
• oral cavity
• hypopharynx
• larynx

• metastatic or unresectable, locally recurrent
• Phase 2 cohort 1: 1L
• • arm A: magrolimab + pembrolizumab + platinum + 5-FU
  • arm B: pembrolizumab + platinum + 5-FU
• Phase 2 cohort 3: 2-3L
• • magrolimab + docetaxel

COLIPAN: collection of Liquid Biopsies in Pancancer patients

H&N plaveiselcelCa

• Liquid Biopsy collection new diagnoses NO NET-tumours

• 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

• 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.

• Liquid Biopsy collection new diagnoses No NET-tumours 

• Prior SOC
• Anti-PD-(L)1 as last line for which progression within 12 weeks from last dose

• randomization between IFX-1 monotherapy (IV) or IFX-1 with pembrolizumab
• mandatory baseline biopsy 

• EGFR Exon 19del or Exon 21 L858R mutation
• osimertinib as 1L (or second line after 1st/2nd gen EGFR TKI)
• Randomization 2:2:1
• Arm A: Lazertinib + Amivantamab + Pemetrexed + Carboplatin
• Arm B: Pemetrexed + Carboplatin
• Arm C: Amivantamab + Pemetrexed + Carboplatin

• 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+ in >=50% tumor cells (centrally assessed)
• 1 prior platinum chemotherapy + 1 checkpoint inhibitor (+ targeted therapy if indicated)
• No previous corneal disorder
• Contact lenses are not permitted

NSCLC

• c-Met+ assessed by IHC (central)
• prior chemotherapy (one line) 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

• CEACAM5 IHC assessed through CARMEN-LC03 trial
• Circulating CEA ≥100 ng/mL
• Prior platinum chemotherapy + checkpoint inhibitor, but no more than 2 prior chemotherapies (+ targeted therapy if indicated)
• no previous corneal disorder
• contact lenses are not permitted

NCT05245071 

NSCLC

• stage IV at time of enrollment
• prior platinum + anti-PD-(L)1
• Patients with EGFR, ALK, or any other known actionable genomic alternations must have also received treatment with at least 1 approved TKI 

NCT05089734 

NSCLC and healty subjects

• Adeno and squamous
• Healthy subjects:
• never smoked or stopped >20y and no COPD
• smoker >20 PY
• Blood and urine collection
• Tissue from patients only
• Sample collection before start 1L

NSCLC stage III, T1c-T3N0M0

• PD-L1 TC ≥ 1% assessed centrally during pre-screening while on cCRT
• Must have not progressed following cCRT
• Must have received at least 2 cycles of chemotherapy
• Total dose of radiation of 60 Gy ± 10% 

NSCLC IB-IIIA

• RET fusion on PCR/NGS
• Must have received definitive locoregional therapy
• Max 10 weeks between local therapy and randomization
• Max 26 weeks between adj chemo and randomization
• Crossover possible

NSCLC

• KRAS G12C
• Cohort 1: PD-L1 TPS <1%
• Cohort 2: PD-L1 TPS ≥1% (CLOSED)
• Unresectable or metastatic
• Squamous or nonsquamous

NSCLC

• T1 to T3N0M0
• Medically inoperable or surgery refusal
• Central or peripheral lesions are eligible
• (Meta)synchronous NSCLC tumors are allowed (max 2)
• NSCLC with sensitizing EGFRm may be eligible for osimertinib cohort:
• • osimertinib after SBRT (no durvalumab)
  • Ex19del or L858R

Malignant Pleural Mesothelioma

• High-Dose RT, Lung-sparing multimodality therapy
• R0-R1 resection
• >18 years
• WHO 0-2
• DLCO > 40%

SCLC, any stage

• Stage I-IV
• Randomization within 16 weeks after last chemo
• Immunotherapy continuing adjuvant is allowed
• No brain metastases and no prior brain RT

NSCLC adenoCa,

NSCLC plaveiselcelCa

• Liquid Biopsy collection new diagnoses No NET tumors 

NSCLC

• Prior platinum + I/O
• Crossover possible