On January 18, 2024 Novocure (NASDAQ: NVCR) reported that its Premarket Approval (PMA) application seeking approval for the use of Tumor Treating Fields (TTFields) therapy together with standard systemic therapies for the treatment of non-small cell lung cancer (NSCLC), following progression on or after platinum-based therapy, has been accepted for filing by the U.S. Food and Drug Administration (FDA) (Press release, NovoCure, JAN 18, 2024, View Source [SID1234639346]).

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"We are thrilled to announce the FDA has accepted our PMA application for review of the LUNAR data in NSCLC," said Asaf Danziger, Novocure’s Chief Executive Officer. "This significant milestone brings us one step closer to treating patients seeking treatment for NSCLC, post-platinum, for which very few effective non-toxic options exist today. I would like to thank our investigators and patients, as well as our Novocure colleagues, for their dedication in pursuit of bringing our novel therapy to thousands of patients in need."

The PMA application for LUNAR was submitted with a filing date of December 15, 2023, and is now under substantive review by the FDA. Novocure expects to receive a regulatory decision from FDA in second half 2024.

About LUNAR

LUNAR tested the safety and effectiveness of TTFields therapy when used together with either an immune checkpoint inhibitor (ICI) or docetaxel for the treatment of patients diagnosed with metastatic NSCLC following progression on or after the use of platinum-based therapy. Patients randomized to receive TTFields therapy together with standard therapies (n=137) demonstrated median overall survival (OS) of 13.2 months compared to 9.9 months in patients treated with standard therapies alone (n=139). Patients randomized to receive TTFields therapy and physician’s choice ICI (n=66) demonstrated a median OS of 18.5 months versus a median OS of 10.8 months in patients treated with an ICI alone (n=68; HR=0.63; P=0.03). Patients randomized to receive TTFields therapy and docetaxel (n=71) had a positive survival trend with a median OS of 11.1 months vs 8.7 months in patients treated with docetaxel alone (n=71). TTFields therapy was well-tolerated with no added systemic toxicities and few grade 3 (no grade 4 or 5) device-related adverse events.

About NSCLC

Lung cancer is the most common cause of cancer-related death worldwide, and NSCLC accounts for approximately 85% of all lung cancers. It is estimated that approximately 193,000 patients are diagnosed with NSCLC each year in the U.S. Physicians use different combinations of surgery, radiation and pharmacological therapies to treat NSCLC, depending on the stage of the disease. Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease. Since 1991, radiation with a combination of platinum-based chemotherapy drugs has been the first-line standard of care for locally advanced or metastatic NSCLC. Certain immune checkpoint inhibitors have been approved for the first-line treatment of NSCLC and the standard of care in this setting appears to be evolving rapidly. The standard of care for second-line treatment is also evolving and may include platinum-based chemotherapy for patients who received immune checkpoint inhibitors as their first-line regimen, docetaxel, immune checkpoint inhibitors or pemetrexed.

On January 18, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported that new data on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s 2024 Gastrointestinal Cancers Symposium (ASCO GI), taking place January 18 – 20, 2024 in San Francisco, California (Press release, Natera, JAN 18, 2024, View Source [SID1234639345]).

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Natera and its collaborators will present 11 abstracts that feature new Signatera data across various GI indications, including two oral presentations. An updated analysis from the previously published GALAXY study, the observational arm of the prospective CIRCULATE-Japan trial, will be presented in an oral presentation at the symposium and is also featured in ASCO (Free ASCO Whitepaper) GI’s press program. GALAXY is one of the largest and most comprehensive prospective studies of MRD testing in resectable colorectal cancer (CRC).

Additionally, the first read-out from the Natera-sponsored BESPOKE CRC study will be presented in a rapid oral presentation. BESPOKE CRC is the first large, prospective, US-based study in resectable CRC, with over 130 participating sites.

Highlights from the abstracts selected for oral presentation include:

Abstract ID: 6 | Oral Abstract Session C | CRC | Presenter: Hiroki Yukami, MD
Circulating tumor DNA (ctDNA) dynamics in CRC patients (pts) with MRD: Updated analysis from GALAXY study in CIRCULATE-JAPAN

This latest analysis from GALAXY included close to 3,000 stage I-IV CRC patients. Key findings include:

ctDNA dynamics at the six-month time point post-surgery showed that patients who remained ctDNA-positive were >6 times more likely to recur compared to those who cleared their ctDNA.
ctDNA-positive patients with sustained clearance in subsequent time points as a result of adjuvant chemotherapy (ACT) had remarkably better outcomes compared to those with transient ctDNA clearance (24-month DFS rate; 90.1% vs 2.3%) or no clearance (24-month DFS rate; 90.1% vs 2%).
In ctDNA-positive patients treated with ACT, a >50% decrease in ctDNA MTM/mL levels at six months, including those with complete clearances, was associated with better DFS than a <50% decrease or increase (24-month DFS rate; 51.1% vs 29%).
Abstract ID: 9 | Rapid Oral Abstract Session C | CRC | Presenter: Pashtoon Kasi, MD, MS
ctDNA for informing adjuvant chemotherapy (ACT) in stage II/III CRC: Interim analysis of BESPOKE CRC study

This analysis included 689 patients with stage II/III resectable CRC. Key findings include:

Within the ctDNA-positive cohort, patients receiving ACT had significantly longer DFS compared to those in the observation group (24-month DFS rate; 42.4% vs 12.5%). No benefit of ACT was observed in ctDNA-negative patients.
ctDNA monitoring allowed for oligometastases-directed therapy in 40% of patients who recurred.
A separate poster on the BESPOKE CRC study (abstract ID: 54) found that in 400+ patients surveyed, ≥92% valued the information received from their Signatera results or would use Signatera to guide their clinical care. In addition, 73% reported that Signatera results reduced anxiety about cancer recurrence.
"These latest findings from the landmark CIRCULATE trial underscore Signatera’s ability to identify patients who may be more likely to benefit from adjuvant chemotherapy, showing the value of personalized MRD testing to guide treatment decisions in CRC and potentially spare patients from unnecessary toxicity," said Hiroki Yukami, MD, from the Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, and lead study author of the GALAXY study. "We are encouraged by the widespread attention and recognition this presentation has received from the oncology community, and are optimistic that the GALAXY study, along with the ALTAIR escalation and VEGA de-escalation arms of CIRCULATE, will fundamentally change the way CRC is treated."

"We are pleased to share new data from the Japanese-based GALAXY and US-based BESPOKE CRC studies, which further demonstrate the prognostic and predictive power of longitudinal testing with Signatera in resectable colorectal cancer," said Minetta C. Liu, MD, chief medical officer of oncology at Natera. "These two prospective clinical trials provide strong evidence supporting the clinical utility of Signatera to inform adjuvant chemotherapy decisions and facilitate surveillance for cancer recurrence."

Below are the additional Natera poster presentations at ASCO (Free ASCO Whitepaper) GI:

Abstract ID: 54 | CRC | Presenter: Pashtoon Kasi, MD, MS
Patient-reported outcomes from the BESPOKE CRC study
Abstract ID: 27 | CRC | Presenter: Giulia Maddalena, MD
INTERCEPT Program of ctDNA Testing for MRD in CRC: Results from a Prospective Clinical Cohort
Abstract ID: 183 | CRC | Presenter: Hidekazu Oyoshi
Prediction of postoperative recurrence by integrating preoperative ctDNA levels and tumor metastasis volume in pts with CRC with resectable lung or liver metastasis
Abstract ID: 528 | Bile Duct Cancer | Presenter: Woo Jin Choi, MD, PhD
The role of pre-operative ctDNA in resectable intrahepatic cholangiocarcinoma
Abstract ID: 212 | Rectal Cancer | Presenter: Sakti Chakrabarti, MD
Prognostic value of ctDNA testing in rectal cancer pts after neoadjuvant therapy (NAT) and surgery
Abstract ID: 23 | CRC | Presenter: Masaaki Miyo, MD, PhD
Association of ctDNA MRD detection with lymph node metastasis after local excision of pathological T1 CRC: First results from DENEB, a CIRCULATE-Japan GALAXY substudy
Abstract ID: 196 | CRC | Presenter: Andrew Pellatt, MD
Redefining The Prognostic Significance of RAS and BRAF V600E Mutations on Disease Free Survival in CRC Pts in the Era of ct-DNA Defined MRD: Results from the MD Anderson INTERCEPT Program
Abstract ID: 695 | Pancreatic Cancer | Presenter: Ujwal Yanala, MD
Utility of ctDNA for the detection of MRD after curative-intent therapy for pts with localized pancreatic adenocarcinoma (PDAC): A single institution series and meta-analysis
Abstract ID: 214 | CRC | Presenter: Nikolas Naleid, MD
Surveillance of Resected Metastatic Colorectal Cancer Utilizing Circulating DNA
About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On January 18, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported that new data on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s 2024 Gastrointestinal Cancers Symposium (ASCO GI), taking place January 18 – 20, 2024 in San Francisco, California (Press release, Natera, JAN 18, 2024, View Source [SID1234639345]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Natera and its collaborators will present 11 abstracts that feature new Signatera data across various GI indications, including two oral presentations. An updated analysis from the previously published GALAXY study, the observational arm of the prospective CIRCULATE-Japan trial, will be presented in an oral presentation at the symposium and is also featured in ASCO (Free ASCO Whitepaper) GI’s press program. GALAXY is one of the largest and most comprehensive prospective studies of MRD testing in resectable colorectal cancer (CRC).

Additionally, the first read-out from the Natera-sponsored BESPOKE CRC study will be presented in a rapid oral presentation. BESPOKE CRC is the first large, prospective, US-based study in resectable CRC, with over 130 participating sites.

Highlights from the abstracts selected for oral presentation include:

Abstract ID: 6 | Oral Abstract Session C | CRC | Presenter: Hiroki Yukami, MD
Circulating tumor DNA (ctDNA) dynamics in CRC patients (pts) with MRD: Updated analysis from GALAXY study in CIRCULATE-JAPAN

This latest analysis from GALAXY included close to 3,000 stage I-IV CRC patients. Key findings include:

ctDNA dynamics at the six-month time point post-surgery showed that patients who remained ctDNA-positive were >6 times more likely to recur compared to those who cleared their ctDNA.
ctDNA-positive patients with sustained clearance in subsequent time points as a result of adjuvant chemotherapy (ACT) had remarkably better outcomes compared to those with transient ctDNA clearance (24-month DFS rate; 90.1% vs 2.3%) or no clearance (24-month DFS rate; 90.1% vs 2%).
In ctDNA-positive patients treated with ACT, a >50% decrease in ctDNA MTM/mL levels at six months, including those with complete clearances, was associated with better DFS than a <50% decrease or increase (24-month DFS rate; 51.1% vs 29%).
Abstract ID: 9 | Rapid Oral Abstract Session C | CRC | Presenter: Pashtoon Kasi, MD, MS
ctDNA for informing adjuvant chemotherapy (ACT) in stage II/III CRC: Interim analysis of BESPOKE CRC study

This analysis included 689 patients with stage II/III resectable CRC. Key findings include:

Within the ctDNA-positive cohort, patients receiving ACT had significantly longer DFS compared to those in the observation group (24-month DFS rate; 42.4% vs 12.5%). No benefit of ACT was observed in ctDNA-negative patients.
ctDNA monitoring allowed for oligometastases-directed therapy in 40% of patients who recurred.
A separate poster on the BESPOKE CRC study (abstract ID: 54) found that in 400+ patients surveyed, ≥92% valued the information received from their Signatera results or would use Signatera to guide their clinical care. In addition, 73% reported that Signatera results reduced anxiety about cancer recurrence.
"These latest findings from the landmark CIRCULATE trial underscore Signatera’s ability to identify patients who may be more likely to benefit from adjuvant chemotherapy, showing the value of personalized MRD testing to guide treatment decisions in CRC and potentially spare patients from unnecessary toxicity," said Hiroki Yukami, MD, from the Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, and lead study author of the GALAXY study. "We are encouraged by the widespread attention and recognition this presentation has received from the oncology community, and are optimistic that the GALAXY study, along with the ALTAIR escalation and VEGA de-escalation arms of CIRCULATE, will fundamentally change the way CRC is treated."

"We are pleased to share new data from the Japanese-based GALAXY and US-based BESPOKE CRC studies, which further demonstrate the prognostic and predictive power of longitudinal testing with Signatera in resectable colorectal cancer," said Minetta C. Liu, MD, chief medical officer of oncology at Natera. "These two prospective clinical trials provide strong evidence supporting the clinical utility of Signatera to inform adjuvant chemotherapy decisions and facilitate surveillance for cancer recurrence."

Below are the additional Natera poster presentations at ASCO (Free ASCO Whitepaper) GI:

Abstract ID: 54 | CRC | Presenter: Pashtoon Kasi, MD, MS
Patient-reported outcomes from the BESPOKE CRC study
Abstract ID: 27 | CRC | Presenter: Giulia Maddalena, MD
INTERCEPT Program of ctDNA Testing for MRD in CRC: Results from a Prospective Clinical Cohort
Abstract ID: 183 | CRC | Presenter: Hidekazu Oyoshi
Prediction of postoperative recurrence by integrating preoperative ctDNA levels and tumor metastasis volume in pts with CRC with resectable lung or liver metastasis
Abstract ID: 528 | Bile Duct Cancer | Presenter: Woo Jin Choi, MD, PhD
The role of pre-operative ctDNA in resectable intrahepatic cholangiocarcinoma
Abstract ID: 212 | Rectal Cancer | Presenter: Sakti Chakrabarti, MD
Prognostic value of ctDNA testing in rectal cancer pts after neoadjuvant therapy (NAT) and surgery
Abstract ID: 23 | CRC | Presenter: Masaaki Miyo, MD, PhD
Association of ctDNA MRD detection with lymph node metastasis after local excision of pathological T1 CRC: First results from DENEB, a CIRCULATE-Japan GALAXY substudy
Abstract ID: 196 | CRC | Presenter: Andrew Pellatt, MD
Redefining The Prognostic Significance of RAS and BRAF V600E Mutations on Disease Free Survival in CRC Pts in the Era of ct-DNA Defined MRD: Results from the MD Anderson INTERCEPT Program
Abstract ID: 695 | Pancreatic Cancer | Presenter: Ujwal Yanala, MD
Utility of ctDNA for the detection of MRD after curative-intent therapy for pts with localized pancreatic adenocarcinoma (PDAC): A single institution series and meta-analysis
Abstract ID: 214 | CRC | Presenter: Nikolas Naleid, MD
Surveillance of Resected Metastatic Colorectal Cancer Utilizing Circulating DNA
About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On January 18, 2024 BPGbio, Inc. a leading biology-first AI-powered biopharma that focuses on oncology, neurology, and rare diseases, reported new data from a phase 2a clinical trial of its lead candidate, BPM31510, in patients with advanced pancreatic cancers at the annual ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, being held January 18-20, 2024, in San Francisco, Calif (Press release, BPGbio, JAN 18, 2024, View Source [SID1234639344]). The multicenter, open-label, non-randomized study aimed to understand the safety and efficacy of BPM31510 delivered intravenously in conjunction with gemcitabine as a second- or third-line therapy for advanced pancreatic cancer.

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In the phase 2a trial (NCT02650804), 19 patients with refractory pancreatic cancer previously treated with other therapies were enrolled and treated with BPM31510 in combination with gemcitabine. Among study participants, median progression free survival was 7.2 months (range: 3.8 months – 10.5 months), twice the observed median progression free survival (3.6 months) reported in patients receiving treatment with gemcitabine alone.

"BPM31510 offers the potential to alter the microenvironment of pancreatic cancer tumors with very manageable side effects, making it an ideal partner to combine with other systemic therapies," said Madappa Kundranda, M.D., Ph.D., Chief of Division of Cancer Medicine, Banner MD Anderson Cancer Center, who was the principal investigator of the study. "Pancreatic cancer, because it is so often diagnosed at later stages, has proven difficult to treat with traditional approaches, which is what makes the sensitizing effects of BPM31510 so compelling."

"These data have validated the BPM31510 mechanism of action and once again show the success of our biology-first Bayesian AI approach to drug development in the clinic," said Niven Narain, Ph.D., CEO of BPGbio. "We see broad applicability for BPM31510 across many solid tumor cancers given its properties as a chemotherapy and radiation sensitizer, and remain committed to pursuing additional clinical studies in both pancreatic cancer and glioblastoma multiforme to address these critical areas of unmet patient need."

ASCO-GI Presentation Summary
Abstract #: 696
Abstract Title: Predictive Multi-omics Analysis of BPM31510 in Combination with Gemcitabine in a Phase 2 Study of Advanced Pancreatic Ductal Adenocarcinoma (PDAC)
In-Person Session Name: Poster Session B
In-Person Poster Session Date: January 19, 2024 at 12:30-2 p.m.
Presenter: Madappa Kundranda, M.D., Ph.D.

BPM31510 as a treatment for pancreatic cancer has received Orphan Drug Designation from the U.S. Food and Drug Administration. BPM31510 is a proprietary nano-lipid molecule designed to target the tumor microenvironment and induce cancer cell death with minimal toxicity. It does this by modulating mitochondrial oxidative phosphorylation in highly aggressive solid tumors, with a direct effect on the BCL-2 protein family. It is believed to be a sensitizer to other chemotherapies, including gemcitabine, as was tested in this study, as well as radiation.

BPGbio plans to continue to study BPM31510 in pancreatic cancer with a phase 2b study looking at its effect as a first line therapy in combination with gemcitabine. In addition, the company has an ongoing phase 2b trial (NCT04752813) studying BPM31510 in combination with vitamin K and standard chemoradiation therapy in patients with glioblastoma multiforme (GBM).

Narain continued, "As a company, we see BPM31510 as offering promise in many other solid tumor cancers including gastric, esophageal, liver, bladder, and sarcoma, where innovation is critically needed."

About BPM31510

BPM31510 is BPGbio’s lead candidate in late-stage development for glioblastoma multiforme (GBM) and pancreatic cancer. The compound has demonstrated a tolerable safety profile and shown potential clinical benefit in both populations. The mechanism of action of BPM31510 was first validated by data from BPGbio’s NAi Interrogative Biology platform, which suggested that there is a hallmark shift in the tumor microenvironment (TME) induced by BPM31510 which modulates mitochondrial oxidative phosphorylation in highly aggressive tumors.

On January 18, 2024 BostonGene, a leading provider of AI-based molecular and immune profiling solutions provider, reported a collaboration with Prisma Health aimed at advancing the understanding of rare tumors by characterizing the tumor microenvironment (TME), mutational landscape and host immune profiles of patients treated with immune checkpoint inhibitors (Press release, BostonGene, JAN 18, 2024, View Source [SID1234639343]).

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In collaboration with Prisma Health’s Rare Tumor Center, BostonGene will analyze tissue and peripheral blood from rare cancer solid-tumor patients to understand the molecular underpinnings of immune-activating drugs commonly used to enhance a person’s innate mechanisms to fight cancer. BostonGene will perform detailed analyses of primary tumors and immunoprofiling of matched peripheral blood collected during this cohort of the trial, which is currently enrolling patients.

Prisma Health, the largest healthcare system in South Carolina, established its Rare Tumor Center in 2014 with a focus on improved outcomes for patients with rare cancers. By adding AI-powered molecular profiling to its long-running prospective clinical trial on checkpoint inhibitors, Prisma Health’s physician researchers hope to gain a substantially deeper understanding, not just of cancer, but of cancer’s interaction with the surrounding tissue and normal supportive cells. The center is part of the Prisma Health Cancer Institute, which actively participates in more than 300 clinical trials annually.

"BostonGene’s innovative solutions will provide a substantially deeper understanding of the molecular profiles of rare tumor patients, which could help us better determine what therapies work for which patients," said Jeffrey Edenfield, MD, medical director for Prisma Health’s Institute for Translational Oncology Research and founder of its Rare Tumor Center. "We are excited about the opportunity to identify potential molecular markers of treatment response and, in turn, improve patient outcomes."

"We’re honored to collaborate with Prisma Health for this prospective clinical trial," said Nathan Fowler, MD, chief medical officer at BostonGene. "We are confident that our next-generation multi-omics analytics will uncover unique molecular characteristics that can be utilized to personalize treatment plans for patients with rare tumors."

BostonGene’s computational platform integrates genomic, transcriptomic and immunoprofiling data to assess the TME and corresponding host immune status to characterize somatic alterations, gene expression, fusions, tumor heterogeneity, the TME and immunoprofiles.

Visit ClinicalTrials.gov for more information on the protocol, A Phase II Study of Durvalumab (MEDI4736) (Anti-PD-L1 Antibody) in Combination with Tremelimumab (Anti-CTLA-4 Antibody) in Subjects with Advanced Rare Solid Tumors.