A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response

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• Neoplasms 9,365

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 252 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Lead sponsor

Genentech, Inc. is the lead sponsor of 507 studies on the registry; 23 are open to participants now.

Of its 90 completed or terminated interventional studies of FDA-regulated products, 50 (56%) have results posted.

Study arms

• Experimental
  Arm A: Entrectinib

  Participants in this treatment arm must have a positive tumor biomarker result for ROS1 gene fusion.

  Drug: Entrectinib

• Experimental
  Arm B: Inavolisib

  Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.

  Drug: Inavolisib

• Experimental
  Arm C: Alectinib

  Participants in this treatment arm must have a positive tumor biomarker result for ALK rearrangement tumors.

  Drug: Alectinib

• Experimental
  Arm D: Ipatasertib

  Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.

  Drug: Ipatasertib

• Experimental
  Arm E: Atezolizumab + Investigator's Choice of Chemotherapy

  Participants in this treatment arm must have a positive tumor biomarker result for either tumor mutational burden (TMB) high or microsatellite instability (MSI) high/deficient mismatch repair (dMMR).

  Drug: Atezolizumab · Drug: Investigator's Choice of Chemotherapy

• Experimental
  Arm F: Trastuzumab Emtansine + Atezolizumab

  Participants in this treatment arm must have a positive tumor biomarker result for human epidermal growth factor receptor 2 (HER2) mutations or amplification without known TMB high or MSI high/dMMR.

  Drug: Atezolizumab · Drug: Trastuzumab Emtansine

• Experimental
  Arm G: PH FDC SC

  Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.

  Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf

• Experimental
  Arm H: PH FDC SC + Investigator's Choice of Chemotherapy

  Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.

  Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf · Drug: Investigator's Choice of Chemotherapy

• Experimental
  Arm I: Trastuzumab Emtansine + Tucatinib

  Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.

  Drug: Trastuzumab Emtansine · Drug: Tucatinib

• Experimental
  Arm J: Trastuzumab Emtansine + Atezolizumab

  Participants in this treatment arm must have positive tumor biomarker results for HER2 mutation or amplification and TMB high or MSI high/dMMR.

  Drug: Atezolizumab · Drug: Trastuzumab Emtansine

• Experimental
  Arm K: Ipatasertib + Atezolizumab

  Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.

  Drug: Ipatasertib · Drug: Atezolizumab

• Experimental
  Arm L: Ipatasertib + Atezolizumab

  Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.

  Drug: Ipatasertib · Drug: Atezolizumab

• Experimental
  Arm M: Ipatasertib + Paclitaxel

  Participants in this treatment arm must have a positive tumor biomarker results for PI3KCA activating mutations and either AKT1/2/3 activating mutation or PTEN loss/loss of function.

  Drug: Ipatasertib · Drug: Paclitaxel

• Experimental
  Arm N: Atezolizumab + Tiragolumab

  Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR.

  Drug: Atezolizumab · Drug: Tiragolumab

• Experimental
  Arm O: Pralsetinib

  Participants in this treatment arm must have a positive tumor biomarker result for RET fusion.

  Drug: Pralsetinib

Interventions

• DrugEntrectinib

  Entrectinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 600 milligrams (mg) per day once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.

  Also known as: Rozlytrek™, RG6268, RO7102122

• DrugInavolisib

  Inavolisib will be self-administered by participants orally at home (except on clinic days) at the same time each day, on a starting dose of 9 mg/day QD until disease progression, intolerable toxicity, or consent withdrawal.

  Also known as: GDC-0077, RG6114, RO7113755

• DrugAlectinib

  Alectinib will be self-administered by participants orally at home (except on clinic days), at the same times each day, on a starting dose of 600 mg twice a day (BID) until disease progression, intolerable toxicity, or consent withdrawal.

  Also known as: Alecensa®, RG7853, RO5424802

• DrugIpatasertib

  Ipatasertib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg QD until disease progression, intolerable toxicity, or consent withdrawal.

  Also known as: GDC-0068, RG7440, RO5532961

• DrugAtezolizumab

  Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg for participants on Day 1 of each 21-day cycle until unacceptable toxicity or progressive disease (or loss of clinical benefit).

  Also known as: Tecentriq®, RG7446, RO5541267

• DrugTrastuzumab Emtansine

  Trastuzumab emtansine will be administered at 3.6 mg per kilogram (kg) of body weight by IV infusion every 21 days (unless dose reduction and/or dose delays are required) until disease progression or unacceptable toxicity.

  Also known as: Kadcyla®, RG3502, RO5304020

• DrugPertuzumab, Trastuzumab, and Hyaluronidase-zzxf

  PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab once every 3 weeks.

  Also known as: PHESGO™, PH FDC SC, Fixed dose combination of trastuzumab and pertuzumab administered subcutaneously, RG6264, RO7198574

• DrugTucatinib

  Tucatinib 300 mg will be administered orally BID continuously starting from Cycle 1 Day 1 onwards.

  Also known as: Tukysa™

• DrugInvestigator's Choice of Chemotherapy

  Chemotherapy will consist of docetaxel, paclitaxel, or capecitabine, as determined by the investigator, and will be administered per the respective package insert and institutional guidelines.

• DrugPaclitaxel

  The dose of paclitaxel is 80 mg/m2 administered by IV infusion on Days 1, 8, and 15 of each 28-day cycle. The paclitaxel infusion will be delivered over at least 60 minutes for each dose per institutional guidelines and administered after the oral dose of ipatasertib.

• DrugTiragolumab

  Following the administration of atezolizumab and an observation period, participants will receive 600 mg tiragolumab at a fixed dose administered by IV infusion on Day 1 of each 21-day cycle.

  Also known as: RG6058, RO7092284, MTIG7192A

• DrugPralsetinib

  Pralsetinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg/day (four 100-mg capsules per day) once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.

  Also known as: GAVRETO™, RG6396, RO7499790

Primary outcomes

1. Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors

   Confirmed objective response rate (cORR)=percentage of participants with best response as complete response (CR) or partial response (PR) for measurable disease \& CR for non-measurable disease. Confirmation=CR/PR on 2 consecutive visits ≥4 weeks apart for 3-week cycles \& ≥6 weeks apart for 4-week cycles. Per RECIST, CR=disappearance of all target lesions. PR= ≥30% decrease in sum of diameters of target lesions, in absence of CR. Per RANO, CR=complete disappearance of all measurable \& non-measurable disease for ≥4 weeks; no new lesions/abnormality on T2/FLAIR imaging; stable/improved non-enhancing lesions; participants must be off corticosteroids or on physiological doses; clinical status stable/improved. PR= ≥50% decrease in the sum of products of perpendicular diameters of measurable enhancing lesions on T2/FLAIR imaging for ≥4 weeks; no progression of non-measurable T1 disease; stable/improved non-enhancing lesions; corticosteroid dose ≤ baseline; clinical status stable/improved.

   Time frame: Up to 32 months

Secondary outcomes

1. Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

   PFS=time from start of treatment to the first occurrence of disease progression (PD) or death from any cause, whichever occurs first, per RECIST v1.1, or RANO. Per RECIST, PD=≥20% increase in sum of diameters of lesions, using the smallest sum during the study as reference, including baseline (BL). Per RANO, PD= ≥25% increase in sum of products of perpendicular diameters of enhancing lesions compared to smallest tumor measurement at BL/best response, on stable/increasing corticosteroids (CS) dose; Significant/ ≥25% increase of T2/FLAIR non-enhancing lesion on stable/increasing CS dose compared to BL/best response after therapy start; Presence of new lesions/increase of enhancement; Clear progression of non-measurable disease; Definite clinical deterioration only due to tumor/decrease in CS dose; Failure to return for evaluation due to death/deterioration. Kaplan-Meier methodology was used to estimate PFS; patients without an event were censored on the last available assessment day.

   Time frame: Time from start of treatment to the first occurrence of disease progression or death from any cause (Up to 32 months)

2. Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

   DOR was defined as the time from the date of the first confirmed complete response (CR) or partial response (PR) to disease progression (PD) or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. CR \& PR were defined per RECIST or RANO as outlined in the description for the cORR outcome measure (OM). PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Kaplan-Meier methodology was used to estimate the median DOR. The 95% confidence intervals for the median DOR were computed by the method of Brookmeyer and Crowley. Participants who did not experience death or PD were censored on the day of the last available assessment.

   Time frame: Time from the date of the first confirmed CR/PR to PD or death from any cause (Up to 32 months)

3. PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

   The PFS rates were calculated using the Kaplan-Meier (KM) method to estimate the percent survival probability of participants (i.e., PFS event-free: did not experience PD or death from any cause) in each treatment arm at landmark timepoints. The 95% confidence intervals for each PFS rate were computed by the method of Greenwood. PFS was defined as the time from the start of study treatment to the first occurrence of PD or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Participants who did not experience death or PD were censored on the day of the last available assessment. The number analyzed per landmark timepoint actually represents the number of participants who remained at risk of experiencing a PFS event at that timepoint. Percentages are rounded off to the nearest decimal point.

   Time frame: At Months 3, 6, 9 and 12

4. Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

   Disease control rate was defined as the percentage of participants whose best response was confirmed CR, confirmed PR, or a response of CR, PR, stable disease (SD), or non-CR/non-PD for a minimum of 98 days for 28-day cycle arms or 70 days for 21-day cycle arms after the first treatment date. CR \& PR were defined per RECIST/RANO as outlined in the description for the cORR OM. SD per RECIST: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. SD per RANO: Participant does not qualify for CR, PR, or minor response or PD; Stable non-enhancing (T2/FLAIR) lesions or abnormalities on same or lower dose of corticosteroids compared to baseline; No new lesions or new T2 or FLAIR abnormalities apart from those consistent with radiation effect, \& no new or increased enhancement; Participants on a should be corticosteroid dose that is not greater than dose at baseline scan \& is stable or improved clinically; Clinical status, stable/improved.

   Time frame: Up to 32 months

5. Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)

   An AE is an untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with the product. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to it. AEs were graded for severity according to NCI CTCAE v5.0. Grade 1= Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3 = Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4= Life-threatening consequences/urgent intervention indicated; Grade 5= Death related to adverse event.

   Time frame: From initiation of study drug until 28 days after the final dose of study drugs other than atezolizumab and until 90 days after the final dose of atezolizumab (Up to 32 months)

Baseline characteristics

Study documents

• Study protocol · Feb 28, 2023
• Statistical analysis plan · Oct 21, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing