praluzatamab ravtansine (CX-2009) / CytomX, AbbVie - LARVOL DELTA

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=125 | Completed | Sponsor: CytomX Therapeutics | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

PROCLAIM-CX-2009: A Trial to Find Safe and Active Doses of an Investigational Drug CX-2009 for Patients With Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=99 | Terminated | Sponsor: CytomX Therapeutics | Completed ➔ Terminated; Covid Pandemic; Business Decision to separate Phase 2 to new study

Metastases • Trial termination • Breast Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

CytomX Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "Research and development expenses decreased by $14.0 million during the three months ended September 30, 2023, to $16.4 million, compared to $30.4 million for the corresponding period in 2022. The reduction in research and development expenses was primarily due to a decrease in personnel related expenses, as well as winding down of laboratory contract services and clinical study activities related to the CX-2009 and CX-2029 programs, partially offset by an increase in laboratory contract services related to IND enabling activities."

Commercial • Oncology

[VIRTUAL] A Phase 2, open-label study to evaluate the safety and efficacy of the probody therapeutic (Pb-Tx) CX‑2009 in metastatic HR-Positive/HER2-negative breast cancer (mHR+/HER2− BC) and of CX-2009 as monotherapy and in combination therapy with CX-072 in metastatic triple-negative breast cancer (TNBC) (SABCS 2020) - "This trial is actively enrolling. Email address for questions or comments: gpaton@cytomx.com"

Clinical • Combination therapy • IO Biomarker • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

CD166-DM4 probody drug conjugate (CX-2009) treatment of 198 patient-derived xenograft models (PDX) in a mouse clinical trial format (AACR 2019) - P1/2; "Because of the large cohort data set, this effort can potentially inform patient selection for clinical studies based on correlating efficacy with CD166 expression, tumor subtype, tumor growth rate (doubling time), and taxane sensitivity. PROBODY is a trademark of CytomX Therapeutics, Inc."

Preliminary results from a phase 2 study of praluzatamab ravtansine (CX-2009) in patients with advanced breast cancer (ABC) (SABCS 2022) - P2 | "This phase 2 study (NCT04596150) evaluates CX-2009 as monotherapy in patients with advanced HR+/HER2− BC (Arm A) and TNBC (Arm B), and in combination with pacmilimab (a conditionally activated PD-L1) in TNBC (Arm C). Praluzatamab ravtansine demonstrated single-agent activity in unselected heavily pretreated patients with HR+/HER2- ABC. Time to event analyses, such as PFS, were confounded by higher-than-expected toxicity at a starting dose of 7 mg/kg. The toxicity profile was generally consistent with a DM4 payload."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=125 | Active, not recruiting | Sponsor: CytomX Therapeutics | Trial completion date: Sep 2023 ➔ Apr 2023 | Trial primary completion date: Sep 2023 ➔ Apr 2023

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

CytomX Therapeutics to Present Phase 2 Data for Praluzatamab Ravtansine (CX-2009) in Patients with Advanced Breast Cancer at the San Antonio Breast Cancer Symposium (Yahoo Finance) - "The poster details the results from patients treated with monotherapy praluzatamab ravtansine for the treatment of advanced HR+/HER2- breast cancer and triple negative breast cancer (TNBC)....Presenting Author: Dr. Kathy Miller..."

CytomX Therapeutics to Present Phase 2 Data for Praluzatamab Ravtansine (CX-2009) in Patients with Advanced Breast Cancer at the San Antonio Breast Cancer Symposium (GlobeNewswire) - P2 | N=125 | NCT04596150 | "CytomX Therapeutics...announced that Phase 2 data for CX-2009, a conditionally activated antibody drug conjugate (ADC) targeting CD166, will be presented at the San Antonio Breast Cancer Symposium on December 8th. The poster details the results from patients treated with monotherapy praluzatamab ravtansine for the treatment of advanced HR+/HER2- breast cancer and triple negative breast cancer (TNBC)."

P2 data • Breast Cancer • Oncology • Solid Tumor

CytomX Therapeutics Reports Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Priorities for 2022-2023:...Provide updated data from the Phase 2 study of praluzatamab ravtansine in advanced breast cancer at the San Antonio Breast Cancer Symposium."

P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab (SABCS 2021) - P2 | "This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with praluzatamab ravtansine as monotherapy and in combination with pacmilimab. This trial is enrolling (NCT04596150)."

Clinical • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=125 | Active, not recruiting | Sponsor: CytomX Therapeutics | Recruiting ➔ Active, not recruiting | N=200 ➔ 125

Combination therapy • Enrollment change • Enrollment closed • Monotherapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

CytomX Therapeutics Reports Second Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Priorities for 2022/2023: (i) Provide a data update for the Phase 2 study of CX-2029 in patients with squamous non-small cell lung cancer in the fourth quarter of 2022; (ii) Provide updated data from the Phase 2 study of praluzatamab ravtansine in advanced breast cancer in the fourth quarter of 2022; (iii) Continue enrolling patients with advanced solid tumors in the Phase 1 study of CX-904."

Enrollment status • P2 data • Breast Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Praluzatamab Ravtansine Generates Responses in HR-Positive, HER2-Negative Breast Cancer (OncLive) - P2 | N=NA | CTMX-2009-002 (NCT04596150) | Sponsor: CytomX Therapeutics | "Praluzatamab ravtansine achieved a promising overall response rate in patients with advanced hormone receptor & positive, HER2-negative breast cancer....Notably, the primary end point was not met in patients with advanced triple-negative breast cancer (TNBC) in arm B, with data showing an ORR of less than 10%. Enrollment will be discontinued in arm B and arm C for patients with TNBC."

Media quote • P2 data

CytomX Therapeutics Announces Phase 2 Results for Praluzatamab Ravtansine in Breast Cancer (GlobeNewswire) - P2 | N=200 | NCT04596150 | Sponsor: CytomX Therapeutics | "CytomX Therapeutics,..announced that the Phase 2 study of praluzatamab ravtansine in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-non-amplified breast cancer (Arm A) met its primary efficacy endpoint of confirmed objective response rate (ORR) of greater than 10 percent by central radiology review....Arm B did not pass protocol-defined futility boundary (ORR was less than 10%) in patients with advanced triple-negative breast cancer (TNBC) and enrollment into Arms B and C will be discontinued."

P2 data • Breast Cancer • Oncology • Solid Tumor

Novel Breast Cancer Drug Meets Main Goal of Eliciting Treatment Responses (Cure Today) - "The study's lead investigator, Dr. Kathy D. Miller...noted, 'In this phase 2 study, praluzatamab ravtansine showed single-agent activity in an unselected population of patients with advanced HR+/HER2-non-amplified breast cancer; additional clinical studies at 6 mg/kg are warranted.'"

Media quote

CytomX Therapeutics Reports First Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Priorities for 2022: Continue enrolling patients with TNBC in Arms B and C in the Phase 2 study of praluzatamab ravtansine and report initial data from Arms A and B in the second half of 2022; Continue advancing the expansion phase of the Phase 2 study of CX-2029 in collaboration with our partner AbbVie and provide a data update in the second half of 2022; Advance the Phase 1 study of CX-904 in solid tumors."

Enrollment status • P2 data • Trial status • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

CTMX-2009-002: Study to Evaluate the Safety and Antitumor Activity of CX-2009 Monotherapy and in Combination With CX-072 in Advanced Breast Cancer (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: CytomX Therapeutics | N=150 ➔ 200 | Trial completion date: Mar 2023 ➔ Sep 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

CytomX Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results, and Provides Business Update (GlobeNewswire) - "Priorities for 2022: (i) Initiate a Phase 1 study of CX-904 in advanced solid tumors in the first half of 2022; (ii) Continue patient enrollment in the expansion phase of the Phase 2 study of CX-2029 and provide additional data updates in the second half of 2022; (iii) Report initial data from Arms A and B in the Phase 2 study of praluzatamab ravtansine in patients with breast cancer in the second half of 2022."

Enrollment status • New P1 trial • P2 data • Breast Cancer • Oncology • Solid Tumor

Praluzatamab ravtansine, a CD166-targeting antibody-drug conjugate, in patients with advanced solid tumors: an open-label phase 1/2 trial. (PubMed, Clin Cancer Res) - "CD166 is a novel, ubiquitously expressed target. CX-2009 is the first conditionally activated antibody-drug conjugate to CD166 to demonstrate both translational and clinical activity in a variety of tumor types."

Journal • P1/2 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Preliminary results of PROCLAIM-CX-2009, a first-in-human, dose-finding study of the Probody drug conjugate CX-2009 in patients with advanced solid tumors (AACR 2019) - P1/2; "Background: CX-2009 is a Probody™ drug conjugate (PDC) directed against CD166 (ubiquitously expressed in normal epithelium and overexpressed in carcinomas) that incorporates DM4, a potent but toxic microtubulin inhibitor (MTI)... CX-2009 was tolerable at dose levels up to 10 mg/kg. Preliminary antitumor activity is observed at dose levels starting at 6 mg/kg and above, warranting further investigation. The study is ongoing, enrolling translational cohorts."

Clinical • Late-breaking abstract • P1 data

[VIRTUAL] CX-2009, a CD166-directed probody drug conjugate (PDC): Results from the first-in-human study in patients (Pts) with advanced cancer including breast cancer (BC). (ASCO 2020) - P1/2 | "Background: CX-2009 is a PROBODY drug conjugate (PDC) directed against CD166 (ALCAM) and conjugated to DM4, a potent microtubule inhibitor (MTI). CX-2009 at 7 mpk is the RP2D on Q3W schedule. Phase II expansion has begun in pts with HR+/HER2- BC. The Q2W schedule will continue to enroll pts to define the RP2D."

Clinical • IO Biomarker • P1 data • Breast Cancer • Fatigue • Gene Therapies • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Keratitis • Lung Cancer • Non Small Cell Lung Cancer • Ocular Inflammation • Oncology • Ophthalmology • Pain • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • HER-2

[VIRTUAL] Intratumoral activation and phase 1/2 clinical activity of CX-2009, a probody drug conjugate (PDC) targeting CD166 (SABCS 2020) - P1/2 | "CX-2009 behaved as designed, with activated drug in tumor and predominantly intact drug in plasma, leading to clinically meaningful disease control in patients with advanced BC. The relationship between normalized intratumoral DM4 and tumor volume changes support the premise that accumulation of payload toxin is related to anti-tumor activity. The correlation between activated CX-2009 and target expression suggests a role for CD166 in intratumoral accumulation of activated CX-2009."

Clinical • P1/2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Triple Negative Breast Cancer • HER-2

[VIRTUAL] Preliminary clinical pharmacokinetics and dose-response to support a phase II dose selection for CX-2009: A masked probody drug conjugate to CD166. (ASCO 2020) - P1/2 | "Preliminary CX-2009 PK data following CX-2009 0.25-10 mpk suggest that CX-2009 circulates predominantly as Intact CX-2009, and that Intact CX-2009 PK is not strongly influenced by target-mediated drug disposition or ADA. Preliminary DR and POPPK simulations support further evaluation of 7 mpk CX-2009 Q3W in selected cohort expansions. Research Funding: CytomX Therapeutics, Inc."

Clinical • P2 data • PK/PD data • Oncology

[VIRTUAL] Phase II, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine (CX 2009) in metastatic HR-positive/HER2 non-amplified breast cancer (mHR+/HER2− BC) and CX-2009 as monotherapy and in combination with pacmilimab in metastatic triple-negative breast cancer (mTNBC) (ESMO-BC 2021) - P2 | "This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with CX-2009 as monotherapy and in combination with pacmilimab. This trial is enrolling (NCT04596150)."

Clinical • Combination therapy • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Oncology • Ophthalmology • Solid Tumor • Triple Negative Breast Cancer • HER-2