Testing Trastuzumab and Pertuzumab in Patients With Higher Than Normal Copies of the HER2 Gene Found in Their Tumors (MATCH - Subprotocol J)

PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, echocardiography (ECHO) at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

• Biopsy Procedure (Procedure), also known as Biopsy, BIOPSY_TYPE, Bx: Undergo biopsy
• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection: Undergo collection of blood samples
• Echocardiography Test (Procedure), also known as EC, Echocardiography: Undergo ECHO
• Pertuzumab (Biological), also known as 2C4, 2C4 Antibody, BCD-178, EG1206A, HLX11, HS627, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, Pertuzumab Biosimilar BCD-178, Pertuzumab Biosimilar EG1206A, Pertuzumab Biosimilar HLX11, Pertuzumab Biosimilar HS627, Pertuzumab Biosimilar TQB2440, Pertuzumab-dpzb, Poherdy, Rhumab 2C4, rhuMAb2C4, RO4368451, TQB 2440, TQB-2440, TQB2440: Given IV
• Radiologic Examination (Procedure), also known as Radiologic Evaluation, Radiologic Exam: Undergo radiologic evaluation
• Trastuzumab (Biological), also known as ABP 980, ALT02, Biceltis, CANMab, CT-P06, CT-P6, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Hercessi, Herclon, Hertraz, Herwenda, Herzuma, HLX 02, HLX-02, HLX02, Kanjinti, Ogivri, Ontruzant, PF 05280014, PF-05280014, PF05280014, QL 1701, QL-1701, QL1701, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, Trastuzumab Biosimilar CT-P6, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar QL1701, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-herw, Trastuzumab-pkrb, Trastuzumab-qyyp, Trastuzumab-strf, Trastuzumab-tuzn, Trastuzumab-zerc, Trazimera, Tuznue, Zercepac: Given IV

Primary outcomes

• Objective Response Rate [Tumor assessments occurred at baseline, then every 3 cycles for the first 33 cycles, and every 4 cycles thereafter until disease progression, up to 3 years post registration]: ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.

Secondary outcomes

• 6-month Progression-Free Survival (PFS) Rate [Tumor assessments occurred at baseline, then every 3 cycles for the first 33 cycles, and every 4 cycles thereafter until disease progression, up to 3 years post registration]: Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
• Progression Free Survival [Tumor assessments occurred at baseline, then every 3 cycles for the first 33 cycles, and every 4 cycles thereafter until disease progression, up to 3 years post registration]: PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
* Patients must fulfill all eligibility criteria outlined the MATCH Master Protocol at the time of registration to treatment step (step 1, 3, 5, 7)
* Patients must have HER2 amplification, or another aberration, as determined via the MATCH Master Protocol
* Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
* Patients must have ECHO or multigated acquisition scan (MUGA) within 4 weeks prior to treatment assignment and must not have a left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be >= 50% for the patient to be eligible
* Patients must not have breast cancer, gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma or mixed histology, gastric/GEJ not otherwise specified (NOS) tumors, or colorectal adenocarcinoma
* Patients must not have known hypersensitivity to trastuzumab or pertuzumab or compounds of similar chemical or biologic composition
* Patients must not have received prior anti-HER2 therapies, including trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, afatinib, neratinib, dacomitinib, canertinib
* Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use adequate contraception (hormonal or double barrier method of birth control, abstinence) from one week prior to study treatment starting, during treatment, and for a period of 7 months after the last dose of study treatment

Participant flow

Outcome results

• Objective Response Rate (Primary), Number, percentage of participants: Treatment (Pertuzumab, Trastuzumab) 12 (3.4 to 28.2)
• 6-month Progression-Free Survival (PFS) Rate (Secondary), Number, percentage of participants: Treatment (Pertuzumab, Trastuzumab) 25.3 (10.7 to 40)
• Progression Free Survival (Secondary), Median, months: Treatment (Pertuzumab, Trastuzumab) 3.3 (2 to 4.1)

Adverse events

Time frame: Assessed every 21 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration.

Serious adverse events by term

Other adverse events by term

• Results publication: Connolly RM, Wang V, Hyman DM, Grivas P, Mitchell EP, Wright JJ, Sharon E, Gray RJ, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Wang J, Wisinski KB, Tricoli JV, Conley BA, Harris LN, Arteaga CL, O'Dwyer PJ, Chen AP, Flaherty KT. Trastuzumab and Pertuzumab in Patients with Non-Breast/Gastroesophageal HER2-Amplified Tumors: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol J. Clin Cancer Res. 2024 Apr 1;30(7):1273-1280. doi: 10.1158/1078-0432.CCR-23-0633. PMID 38433347

• Study Protocol (PDF, 2022-11-10)

• Roisin M Connolly, Principal investigator, ECOG-ACRIN Cancer Research Group

NIH grants: U10CA180820