Concierge Trials

Tumor profile: - Treatment history: Residual invasive disease in the breast and/or axillary nodes at surgical resection following at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane (+/- platinum-chemotherapy, +/- pembrolizumab) Performance status: Good (ECOG 0-1)
Treatment history: Residual invasive disease in the breast and/or axillary nodes at surgical resection following at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane (+/- platinum-chemotherapy, +/- pembrolizumab) Performance status: Good (ECOG 0-1)

Allocation: Randomized Intervention
Model: Parallel Assignment Intervention Model Description: Parallel
Masking: None (Open Label) Interventions: Investigational agent, Durvalumab, Capecitabine, Pembrolizumab

Tumor profile: PD-L1 positive tumors (CPS > 10) Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Performance status: Good (ECOG 0-1)
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Performance status: Good (ECOG 0-1)

Allocation: Randomized Intervention
Model: Parallel Assignment Intervention Model Description: Participants will be randomised either 1:1 to Arm 1 (Dato-DXd + durvalumab) and Arm 2 (ICC + pembrolizumab), or in selected countries, 1:1:1 to Arms 1, 2 and 3 (Dato-DXd monotherapy). Once approximately 75 participants are randomised to Arm 3, this cohort will close, and all countries will continue with a 1:1 randomisation strategy for Arms 1 and 2.
Masking: None (Open Label)

Tumor profile: Low HER2 expression (IHC 1+ or 2+/ISH -) Treatment history: Disease progression on a line of therapy including endocrine therapy and a CDK4/6 inhibitor, or 2 previous lines of endocrine therapy, and no prior chemotherapy in the advanced/metastatic setting Performance status: Good (ECOG 0-1)
Treatment history: Disease progression on a line of therapy including endocrine therapy and a CDK4/6 inhibitor, or 2 previous lines of endocrine therapy, and no prior chemotherapy in the advanced/metastatic setting Performance status: Good (ECOG 0-1)

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Tumor profile: Low HER2 expression (IHC 1+ or 2+/ISH -) Treatment history: Disease progression on a line of therapy including endocrine therapy and a CDK4/6 inhibitor, or 2 previous lines of endocrine therapy, and no prior chemotherapy in the advanced/metastatic setting Performance status: Good (ECOG 0-1)
Treatment history: Disease progression on a line of therapy including endocrine therapy and a CDK4/6 inhibitor, or 2 previous lines of endocrine therapy, and no prior chemotherapy in the advanced/metastatic setting Performance status: Good (ECOG 0-1)

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Tumor profile: - Treatment history: Undergone complete macroscopic resection (R0, R1) requiring adjuvant therapy Performance status: Good (ECOG 0-1)
Treatment history: Undergone complete macroscopic resection (R0, R1) requiring adjuvant therapy Performance status: Good (ECOG 0-1)

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Masking Description: Double-blind masking

Tumor profile: Microsatellite stability, proficient mismatch repair MSS/pMMR CMS4 subtype by NGS could be selected for specific studies/cohorts Treatment history: Progression after previous combination chemotherapy, usually fluorouracil-based including oxaliplatin and irinotecan Good performance status: ECOG 0-1
Treatment history: Progression after previous combination chemotherapy, usually fluorouracil-based including oxaliplatin and irinotecan Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Non-Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Tumor profile: Microsatellite stability, proficient mismatch repair MSS/pMMR, No TMB-High Treatment history: Received fluoruracil-based combination chemotherapy regimens including oxciplatin and irinotecan. No progression on more than 2 prior systemic therapies in metastatic setting. Performance status: Good (ECOG 0-1)
Treatment history: Received fluoruracil-based combination chemotherapy regimens including oxciplatin and irinotecan. No progression on more than 2 prior systemic therapies in metastatic setting. Performance status: Good (ECOG 0-1)

Allocation: Non-Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Tumor profile: Microsatellite unstable (MSI-H), Deficient Mismatch Repair (dMMR) Treatment history: Progression after previous combination chemotherapy and PD-1/PD-L1 antagonists Performance status: Good (ECOG 0-1)
Treatment history: Progression after previous combination chemotherapy and PD-1/PD-L1 antagonists Performance status: Good (ECOG 0-1)

Allocation: Non-Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Disease characteristics: Relapsed metastatic colorectal cancer refractory to standard of care or no satisfactory treatment options available Tumor profile: - Treatment history: Progressed on or intolerant to fluoropyrimidine, irinotecan and oxaliplatin-based chemotherapy Performance status: Good (ECOG 0-2)
Tumor profile: - Treatment history: Progressed on or intolerant to fluoropyrimidine, irinotecan and oxaliplatin-based chemotherapy Performance status: Good (ECOG 0-2)
Treatment history: Progressed on or intolerant to fluoropyrimidine, irinotecan and oxaliplatin-based chemotherapy Performance status: Good (ECOG 0-2)

Expanded Access Intervention: Investigational agent

Disease characteristics: Advanced gastrointestinal stromal tumor (GIST) Tumor profile: Co-occurring mutations in KIT exons 11, plus 17 or 18 & no KIT mutations in exons 9, 13 or 14 Treatment history: Progression after only 1 prior systemic line of therapy with imatinib Performance status: Good (ECOG 0-2)
Tumor profile: Co-occurring mutations in KIT exons 11, plus 17 or 18 & no KIT mutations in exons 9, 13 or 14 Treatment history: Progression after only 1 prior systemic line of therapy with imatinib Performance status: Good (ECOG 0-2)
Treatment history: Progression after only 1 prior systemic line of therapy with imatinib Performance status: Good (ECOG 0-2)

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Tumor profile: - Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR progressed following treatment with a platinum-based regimen and PD-1/PD-L1 antagonists; No prior therapy with agents targeting the TGFb signalling pathway Performance status: Good (ECOG 0-1)
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR progressed following treatment with a platinum-based regimen and PD-1/PD-L1 antagonists; No prior therapy with agents targeting the TGFb signalling pathway Performance status: Good (ECOG 0-1)

Allocation: Non-Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Disease characteristics: Locally advanced or metastatic breast cancer, not amenable to therapy with curative intent Tumor profile: Estrogen receptor positive (ER+), HER2 negative (HER2-) Loss of function mutations in genes BRCA1, BRCA2 or PALB2 Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Tumor profile: Estrogen receptor positive (ER+), HER2 negative (HER2-) Loss of function mutations in genes BRCA1, BRCA2 or PALB2 Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Locally advanced or metastatic breast cancer, not amenable to therapy with curative intent Tumor profile: Estrogen receptor positive (ER+), HER2 negative (HER2-) Treatment history: Progressed after prior first-line with endocrine therapy in combination with a CDK4/6 inhibitor Good performance status: ECOG 0-1
Tumor profile: Estrogen receptor positive (ER+), HER2 negative (HER2-) Treatment history: Progressed after prior first-line with endocrine therapy in combination with a CDK4/6 inhibitor Good performance status: ECOG 0-1
Treatment history: Progressed after prior first-line with endocrine therapy in combination with a CDK4/6 inhibitor Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Disease characteristics: Locally advanced or metastatic cholangiocarcinoma Tumor profile: HER2 positive (HER2+) Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Tumor profile: HER2 positive (HER2+) Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Disease characteristics: Head and neck squamous cell carcinoma considered locally advanced with no evidence of distant metastases Tumor profile: HPV positive or negative status Treatment history: Completed standard of care with concurrent chemoradiotherapy (CRT) without disease progression Good performance status: ECOG 0-1
Tumor profile: HPV positive or negative status Treatment history: Completed standard of care with concurrent chemoradiotherapy (CRT) without disease progression Good performance status: ECOG 0-1
Treatment history: Completed standard of care with concurrent chemoradiotherapy (CRT) without disease progression Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Single (Outcomes Assessor)

Disease characteristics: Metastatic or unresectable Head and Neck squamous cell carcinoma Tumor profile: PD-L1 combined positive score (CPS) ≥1 Treatment history: No prior systemic therapy in the recurrent/metastatic setting Good performance status: 0-1
Tumor profile: PD-L1 combined positive score (CPS) ≥1 Treatment history: No prior systemic therapy in the recurrent/metastatic setting Good performance status: 0-1
Treatment history: No prior systemic therapy in the recurrent/metastatic setting Good performance status: 0-1
Good performance status: 0-1

Allocation: Non-Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Disease characteristics: Locally advanced or metastatic hepatocellular carcinoma not amenable to surgical/locoregional therapies Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR Progressed on or after one systemic line of therapy containing or not an immune checkpoint inhibitor (ICI) Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR Progressed on or after one systemic line of therapy containing or not an immune checkpoint inhibitor (ICI) Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A
Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Locally advanced or metastatic hepatocellular carcinoma Tumor profile: - Treatment history: No prior systemic therapy. Not amenable to surgical/locoregional therapies or progressed after those. Good performance status: ECOG 0-1, Child Pugh A-B
Tumor profile: - Treatment history: No prior systemic therapy. Not amenable to surgical/locoregional therapies or progressed after those. Good performance status: ECOG 0-1, Child Pugh A-B
Treatment history: No prior systemic therapy. Not amenable to surgical/locoregional therapies or progressed after those. Good performance status: ECOG 0-1, Child Pugh A-B
Good performance status: ECOG 0-1, Child Pugh A-B

Allocation: Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Disease characteristics: Advanced Hepatocellular carcinoma Tumor profile: - Treatment history: Progression during or after one line of therapy. No prior treatment with anti PD-L1/PD1 and agents targeting the TGF beta signalling pathway. Good performance status: ECOG 0-1, Child Pugh A
Tumor profile: - Treatment history: Progression during or after one line of therapy. No prior treatment with anti PD-L1/PD1 and agents targeting the TGF beta signalling pathway. Good performance status: ECOG 0-1, Child Pugh A
Treatment history: Progression during or after one line of therapy. No prior treatment with anti PD-L1/PD1 and agents targeting the TGF beta signalling pathway. Good performance status: ECOG 0-1, Child Pugh A
Good performance status: ECOG 0-1, Child Pugh A

Allocation: Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Disease characteristics: Locoregional hepatocellular carcinoma without evidence of extrahepatic disease Not amenable to curative surgery or transplantation or curative ablation Amenable to transcatheter arterial chemoembolization (TACE) Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A
Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A

Disease characteristics: Locally advanced or metastatic hepatocellular carcinoma not amenable to surgical/locoregional therapies Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR Progressed on or after one systemic line of therapy containing or not an immune checkpoint inhibitor (ICI) Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR Progressed on or after one systemic line of therapy containing or not an immune checkpoint inhibitor (ICI) Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A
Good performance status: ECOG 0-1 Preserved liver function: Child Pugh A

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Disease characteristics: Metastatic non-small cell lung cancer (NSCLC) not amenable to therapies with curative intent Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR Progression after 1 line of chemotherapy and 1 line of PD-1/PD-L1 antagonists, alone or in combination Good performance status: ECOG 0-1
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting; OR Progression after 1 line of chemotherapy and 1 line of PD-1/PD-L1 antagonists, alone or in combination Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Disease characteristics: Locally advanced or metastatic non-small cell lung cancer (NSCLC) not amenable to therapies with curative intent Tumor profile: C-MET overexpressing tumor Treatment history: Progressed on at least 1 line of systemic therapy for advanced/metastatic cancer Good performance status: ECOG 0-1
Tumor profile: C-MET overexpressing tumor Treatment history: Progressed on at least 1 line of systemic therapy for advanced/metastatic cancer Good performance status: ECOG 0-1
Treatment history: Progressed on at least 1 line of systemic therapy for advanced/metastatic cancer Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Stage I NSCLC of adenocarcinoma histology Disease amenable to surgical resection High risk of recurrence due to either high ctDNA or high-risk pathological factors including high grade, visceral pleural invasion or lymphovascular invasion Treatment history: Complete surgical resection Good performance status: ECOG 0-1
Treatment history: Complete surgical resection Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Disease characteristics: Advanced or metastatic NSCLC not amenable to therapies with curative intent Tumor profile: EGFR sensitizing mutation Treatment history: Progression on Osimertinib as the most recent line of therapy Good performance status: ECOG 0-1
Tumor profile: EGFR sensitizing mutation Treatment history: Progression on Osimertinib as the most recent line of therapy Good performance status: ECOG 0-1
Treatment history: Progression on Osimertinib as the most recent line of therapy Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Disease characteristics: Stage IA2, IA3 NSCLC of non-squamous histology Disease amenable to surgical resection Tumor profile: EGFR most common activating mutations (Ex19del, L858R) Treatment history: Complete surgical resection by lobectomy Good performance status: ECOG 0-1
Tumor profile: EGFR most common activating mutations (Ex19del, L858R) Treatment history: Complete surgical resection by lobectomy Good performance status: ECOG 0-1
Treatment history: Complete surgical resection by lobectomy Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)

Disease characteristics: Locally advanced or metastatic non-small cell lung cancer (NSCLC) of adenocarcinoma histology, not amenable to therapies with curative intent Tumor profile: MDM2 amplifications Treatment history: Previously treated and progressed after treatment with standard of care Good performance status: ECOG 0-1
Tumor profile: MDM2 amplifications Treatment history: Previously treated and progressed after treatment with standard of care Good performance status: ECOG 0-1
Treatment history: Previously treated and progressed after treatment with standard of care Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: N/A Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Non Small Cell Lung Cancer Stages III B, IIC or IV not candidates for definitive therapy Tumor profile: PD-L1 >= 50% No actionable gene mutations. Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Tumor profile: PD-L1 >= 50% No actionable gene mutations. Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Disease characteristics: Locally advanced or metastatic non-small cell lung cancer (NSCLC) not amenable to therapies with curative intent Tumor profile: PD-L1 positive (> 50%) No actionable gene mutations Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Tumor profile: PD-L1 positive (> 50%) No actionable gene mutations Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Treatment history: Previously untreated with systemic lines of therapy in the advanced/metastatic setting Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Disease characteristics: Locally advanced (Stage III) unresectable Non small Cell Lung Cancer Tumor profile: ALK fusion positive. No known EGFR oncogenic driver mutation Treatment history: At least two cycles of platinum-based chemotherapy given as part of cCRT or sCRT without disease progression during therapy. No other prior therapies for NSCLC Good performance status: ECOG 0-2
Tumor profile: ALK fusion positive. No known EGFR oncogenic driver mutation Treatment history: At least two cycles of platinum-based chemotherapy given as part of cCRT or sCRT without disease progression during therapy. No other prior therapies for NSCLC Good performance status: ECOG 0-2
Treatment history: At least two cycles of platinum-based chemotherapy given as part of cCRT or sCRT without disease progression during therapy. No other prior therapies for NSCLC Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Locally advanced (Stage III) unresectable Non Small Cell Lung Cancer Tumor profile: - Treatment history: Planned/receiving/received cCRT or sCRT without disease progression during therapy Good performance status: ECOG 0-2
Tumor profile: - Treatment history: Planned/receiving/received cCRT or sCRT without disease progression during therapy Good performance status: ECOG 0-2
Treatment history: Planned/receiving/received cCRT or sCRT without disease progression during therapy Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: N/A Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Advanced non-resectable or metastatic adult-type granulosa cell tumor of the ovary, not candidates for surgical or radiation therapy with curative intent Treatment history: Progression after at least 1 prior systemic line of therapy. No prior treatment with anti PD-L1/PD1 and agents targeting the TGF beta signalling pathway. Good performance status: ECOG 0-1
Treatment history: Progression after at least 1 prior systemic line of therapy. No prior treatment with anti PD-L1/PD1 and agents targeting the TGF beta signalling pathway. Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Sequential Assignment
Masking: None (Open Label)

Disease characteristics: Advanced or metastatic pancreatic cancer, not amenable to therapy with curative intent Tumor profile: MDM2 amplification expressing tumors could be eligible for specific studies/cohorts Treatment history: Progression on or after at least 1 prior systemic line of therapy considered standard of care Good performance status: ECOG 0-1
Tumor profile: MDM2 amplification expressing tumors could be eligible for specific studies/cohorts Treatment history: Progression on or after at least 1 prior systemic line of therapy considered standard of care Good performance status: ECOG 0-1
Treatment history: Progression on or after at least 1 prior systemic line of therapy considered standard of care Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: N/A Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Recurrent or de novo metastatic prostate adenocarcinoma not amenable to therapy with curative intent Treatment history: Castration sensitive, on androgen deprivation therapy with a GnRH analogue or status-post bilateral orchiectomy without evidence of progression Good performance status: ECOG 0-1
Treatment history: Castration sensitive, on androgen deprivation therapy with a GnRH analogue or status-post bilateral orchiectomy without evidence of progression Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: Randomized Intervention
Model: Parallel Assignment Intervention Model Description: Within each cohort (HRRm and non-HRRm), participants are randomized in 1:1 ratio to one of two treatment arms
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Disease characteristics: Advanced unresectable or metastatic solid tumors not amenable to therapy with curative intent Tumor profile: No specific biomarker alterations; OR Biomarker alterations could make patients eligible for specific studies/cohorts: ROS1 fusion, NTRK 1/2/3 fusion, ALK fusion, KRAS G12C mutation, ATM biallelic loss of function alterations, SETD2 biallelic loss of function alterations Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: ECOG 0-2
Tumor profile: No specific biomarker alterations; OR Biomarker alterations could make patients eligible for specific studies/cohorts: ROS1 fusion, NTRK 1/2/3 fusion, ALK fusion, KRAS G12C mutation, ATM biallelic loss of function alterations, SETD2 biallelic loss of function alterations Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: ECOG 0-2
Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Advanced unresectable or metastatic solid tumors not amenable to therapy with curative intent Tumor profile: No specific biomarker alterations; OR Biomarker alterations could make patients eligible for specific studies/cohorts: ROS1 fusion, NTRK 1/2/3 fusion, ALK fusion, KRAS G12C mutation, ATM biallelic loss of function alterations, SETD2 biallelic loss of function alterations Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: ECOG 0-2
Tumor profile: No specific biomarker alterations; OR Biomarker alterations could make patients eligible for specific studies/cohorts: ROS1 fusion, NTRK 1/2/3 fusion, ALK fusion, KRAS G12C mutation, ATM biallelic loss of function alterations, SETD2 biallelic loss of function alterations Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: ECOG 0-2
Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Advanced unresectable or metastatic solid tumors not amenable to therapy with curative intent Tumor profile: No specific biomarker alterations; OR Biomarker alterations could make patients eligible for specific studies/cohorts: ALK fusion Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: Lansky Performance Status >= 50% if < 16 years, or Karnofsky Performance Status >= 50% if 16-18 years
Tumor profile: No specific biomarker alterations; OR Biomarker alterations could make patients eligible for specific studies/cohorts: ALK fusion Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: Lansky Performance Status >= 50% if < 16 years, or Karnofsky Performance Status >= 50% if 16-18 years
Treatment history: Disease progression after standard of care or no available acceptable options Good performance status: Lansky Performance Status >= 50% if < 16 years, or Karnofsky Performance Status >= 50% if 16-18 years
Good performance status: Lansky Performance Status >= 50% if < 16 years, or Karnofsky Performance Status >= 50% if 16-18 years

Allocation: N/A Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Locally advanced or metastatic urothelial cancer, not amenable to therapy with curative intent Tumor profile: MDM2 amplification Treatment history: Disease progression after standard of care Good performance status: ECOG 0-1
Tumor profile: MDM2 amplification Treatment history: Disease progression after standard of care Good performance status: ECOG 0-1
Treatment history: Disease progression after standard of care Good performance status: ECOG 0-1
Good performance status: ECOG 0-1

Allocation: N/A Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Light chain amyloidosis (AL) with cardiac involvement Mayo stage IV Treatment history: Treatment naïve, not eligible for ASCT Good performance status: ECOG 0-2
Treatment history: Treatment naïve, not eligible for ASCT Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Disease characteristics: Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL) Treatment history: Relapsed/refractory to 2 or more prior lines of therapy Prior treatment with a BTK inhibitor Good performance status: ECOG 0-2
Treatment history: Relapsed/refractory to 2 or more prior lines of therapy Prior treatment with a BTK inhibitor Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL) with Richter’s transformation to DLBCL Treatment history: Relapsed/refractory to 1 or more prior lines of therapy administered for Richter’s transformation Prior treatment with a BTK inhibitor Good performance status: ECOG 0-2
Treatment history: Relapsed/refractory to 1 or more prior lines of therapy administered for Richter’s transformation Prior treatment with a BTK inhibitor Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Diffuse large B-cell lymphoma (DLBCL), not germinal center type Treatment history: Relapsed/refractory to 2 or more prior lines of therapy administered for Richter’s transformation Prior treatment with an anthracycline-based and an anti-CD20 based regimen Good performance status: ECOG 0-2
Treatment history: Relapsed/refractory to 2 or more prior lines of therapy administered for Richter’s transformation Prior treatment with an anthracycline-based and an anti-CD20 based regimen Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Diffuse large B-cell lymphoma (DLBCL), Ann Arbor stage II-IV Treatment history: Not eligible for anthracycline-based therapy or cytotoxic chemotherapy Good performance status: ECOG 0-2
Treatment history: Not eligible for anthracycline-based therapy or cytotoxic chemotherapy Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Follicular lymphoma (FL), grade 1, 2 or 3a, with active disease requiring treatment Treatment history: Relapsed/refractory to 2 or more prior lines of therapy At least 1 prior line of therapy containing an anti-CD20 monoclonal antibody Good performance status: ECOG 0-2
Treatment history: Relapsed/refractory to 2 or more prior lines of therapy At least 1 prior line of therapy containing an anti-CD20 monoclonal antibody Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Follicular lymphoma (FL), stage II bulky, III or IV requiring treatment due to B symptoms, large tumor mass or lymphoma-related complications Treatment history: No prior treatment with any systemic anti-lymphoma therapy Good performance status: ECOG 0-2
Treatment history: No prior treatment with any systemic anti-lymphoma therapy Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Follicular lymphoma Stage II bulky, III or IV requiring treatment due to B symptoms, large tumor mass or lymphoma-related complications Tumor profile: - Treatment history: No prior treatment with any systemic anti-lymphoma therapy, or relapsed/refractory who have not received R-CHOP or R-CVP Good performance status: ECOG 0-2
Tumor profile: - Treatment history: No prior treatment with any systemic anti-lymphoma therapy, or relapsed/refractory who have not received R-CHOP or R-CVP Good performance status: ECOG 0-2
Treatment history: No prior treatment with any systemic anti-lymphoma therapy, or relapsed/refractory who have not received R-CHOP or R-CVP Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Mantle cell lymphoma (MCL) with active disease requiring treatment Treatment history: Prior treatment with anti-CD20 monoclonal antibody and one BTK inhibitor therapy Good performance status: ECOG 0-2
Treatment history: Prior treatment with anti-CD20 monoclonal antibody and one BTK inhibitor therapy Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: N/A Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Mantle cell Lymphoma relapsed or refractory to 2 or more prior lines of therapy. Tumor profile: - Treatment history: Previously treated with a covalently binding BTK inhibitor (ibrutinib, acalabrutinib or zanubrutinib) and anti-CD20 monoclonal antibody Good performance status: ECOG 0-2
Tumor profile: - Treatment history: Previously treated with a covalently binding BTK inhibitor (ibrutinib, acalabrutinib or zanubrutinib) and anti-CD20 monoclonal antibody Good performance status: ECOG 0-2
Treatment history: Previously treated with a covalently binding BTK inhibitor (ibrutinib, acalabrutinib or zanubrutinib) and anti-CD20 monoclonal antibody Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Marginal zone lymphoma (MZL) with active disease requiring treatment Treatment history: Relapsed/refractory to 2 or more prior lines of therapy Prior treatment with anti-CD20 monoclonal antibody and one BTK inhibitor therapy Good performance status: ECOG 0-2
Treatment history: Relapsed/refractory to 2 or more prior lines of therapy Prior treatment with anti-CD20 monoclonal antibody and one BTK inhibitor therapy Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Single Group Assignment
Masking: None (Open Label)

Disease characteristics: Multiple myeloma (MM) Treatment history: Lines of therapy: Prior therapy with 1 to 3 lines of anti-myeloma therapy including lenalidomide; OR Prior therapy with at least 1 anti-myeloma therapy including lenalidomide and an antiCD-38 agent; OR Prior therapy at least 1 line of anti-myeloma therapy including lenalidomide and a proteasome inhibitor Progression documented after last therapy Minimal response or better to at least 1 prior anti-myeloma therapy Good performance status: ECOG 0-2
Treatment history: Lines of therapy: Prior therapy with 1 to 3 lines of anti-myeloma therapy including lenalidomide; OR Prior therapy with at least 1 anti-myeloma therapy including lenalidomide and an antiCD-38 agent; OR Prior therapy at least 1 line of anti-myeloma therapy including lenalidomide and a proteasome inhibitor Progression documented after last therapy Minimal response or better to at least 1 prior anti-myeloma therapy Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Multipe myeloma (MM) Tumor profile: - Treatment history: Prior treatment with at least 1 line of therapy including lenalidomide and anti CD-38. No prior treatment with mezigdomide or carfilzomib. Good performance status: ECOG 0-2
Tumor profile: - Treatment history: Prior treatment with at least 1 line of therapy including lenalidomide and anti CD-38. No prior treatment with mezigdomide or carfilzomib. Good performance status: ECOG 0-2
Treatment history: Prior treatment with at least 1 line of therapy including lenalidomide and anti CD-38. No prior treatment with mezigdomide or carfilzomib. Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Multiple myeloma (MM) Treatment history: Treatment naïve Good performance status: ECOG 0-2
Treatment history: Treatment naïve Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Sequential Assignment Intervention Model Description: Note: Phase 1 part B will be randomized 1:1. All other participants will be non-randomized.

Disease characteristics: Multiple myeloma (MM) Treatment history: Lines of therapy: Prior therapy with 1 to 3 lines of anti-myeloma therapy including lenalidomide; OR Prior therapy with at least 1 anti-myeloma therapy including lenalidomide and an antiCD-38 agent; OR Prior therapy at least 1 line of anti-myeloma therapy including lenalidomide and a proteasome inhibitor Progression documented after last therapy Minimal response or better to at least 1 prior anti-myeloma therapy Good performance status: ECOG 0-2
Treatment history: Lines of therapy: Prior therapy with 1 to 3 lines of anti-myeloma therapy including lenalidomide; OR Prior therapy with at least 1 anti-myeloma therapy including lenalidomide and an antiCD-38 agent; OR Prior therapy at least 1 line of anti-myeloma therapy including lenalidomide and a proteasome inhibitor Progression documented after last therapy Minimal response or better to at least 1 prior anti-myeloma therapy Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: None (Open Label)

Disease characteristics: Multiple Myeloma (MM) Tumor profile: - Treatment history: At least 1 prior line of antimyeloma therapy including lenalidomide and proteasome inhibitor (PI). No prior treatment with pomalidomide. Good performance status: ECOG 0-2
Tumor profile: - Treatment history: At least 1 prior line of antimyeloma therapy including lenalidomide and proteasome inhibitor (PI). No prior treatment with pomalidomide. Good performance status: ECOG 0-2
Treatment history: At least 1 prior line of antimyeloma therapy including lenalidomide and proteasome inhibitor (PI). No prior treatment with pomalidomide. Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: No information
Masking: Open label

Disease characteristics: Primary myelofibrosis, post essential thrombocytopenia myelofibrosis, or post polycythemia vera myelofibrosis Transfusion dependent of pRBC Treatment history: On treatment with a stable dose of a JAK2 inhibitor Good performance status: ECOG 0-2
Treatment history: On treatment with a stable dose of a JAK2 inhibitor Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Randomized Intervention
Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)

Disease characteristics: Waldenstrom macroglobulinemia (WM) with active disease requiring treatment Treatment history: Relapsed/refractory to 2 or more prior lines of therapy Prior treatment with anti-CD20 monoclonal antibody Good performance status: ECOG 0-2
Treatment history: Relapsed/refractory to 2 or more prior lines of therapy Prior treatment with anti-CD20 monoclonal antibody Good performance status: ECOG 0-2
Good performance status: ECOG 0-2

Allocation: Non-Randomized Intervention
Model: Single Group Assignment
Masking: None (Open Label)